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Immune responses during cutaneous and visceral leishmaniasis

Published online by Cambridge University Press:  30 July 2014

LUKASZ KEDZIERSKI*
Affiliation:
Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Pde, Parkville 3052, Victoria, Australia Department of Medical Biology, University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia
KRYSTAL J. EVANS
Affiliation:
Department of Medical Biology, University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Pde, Parkville 3052, Victoria, Australia
*
*Corresponding author: Walter and Eliza Hall Institute of Medical Research, 1G Royal Pde, Parkville 3052, Victoria, Australia. E-mail: [email protected]

Summary

Leishmania are protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world, resulting in an estimated 1·3 million new cases and 30 000 deaths annually. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective in several endemic regions. To date there is no vaccine against leishmaniasis, although extensive evidence from studies in animal models indicates that solid protection can be achieved upon immunization. This review focuses on immune responses to Leishmania in both cutaneous and visceral forms of the disease, pointing to the complexity of the immune response and to a range of evasive mechanisms utilized by the parasite to bypass those responses. The amalgam of innate and acquired immunity combined with the paucity of data on the human immune response is one of the major problems currently hampering vaccine development and implementation.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2014 

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References

REFERENCES

Ahmed, S., Colmenares, M., Soong, L., Goldsmith-Pestana, K., Munstermann, L., Molina, R. and McMahon-Pratt, D. (2003). Intradermal infection model for pathogenesis and vaccine studies of murine visceral leishmaniasis. Infection and Immunity 71, 401410.Google Scholar
Ajdary, S., Alimohammadian, M. H., Eslami, M. B., Kemp, K. and Kharazmi, A. (2000). Comparison of the immune profile of nonhealing cutaneous leishmaniasis patients with those with active lesions and those who have recovered from infection. Infection and Immunity 68, 17601764.Google Scholar
Alexander, C. E., Kaye, P. M. and Engwerda, C. R. (2001). CD95 is required for the early control of parasite burden in the liver of Leishmania donovani-infected mice. European Journal of Immunology 31, 11991210.Google Scholar
Alexander, J., Brombacher, F., McGachy, H. A., McKenzie, A. N., Walker, W. and Carter, K. C. (2002). An essential role for IL-13 in maintaining a non-healing response following Leishmania mexicana infection. European Journal of Immunology 32, 29232933.Google Scholar
Ali, A. (2002). Leishmaniases and HIV/AIDS co-infections: review of common features and management experiences. Ethiopian Medical Journal 40 (Suppl. 1), 3749.Google Scholar
Amprey, J. L., Im, J. S., Turco, S. J., Murray, H. W., Illarionov, P. A., Besra, G. S., Porcelli, S. A. and Spath, G. F. (2004). A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan. Journal of Experimental Medicine 200, 895904. doi: 10.1084/jem.20040704.Google Scholar
Anam, K., Afrin, F., Banerjee, D., Pramanik, N., Guha, S. K., Goswami, R. P., Saha, S. K. and Ali, N. (1999). Differential decline in Leishmania membrane antigen-specific immunoglobulin G (IgG), IgM, IgE, and IgG subclass antibodies in Indian kala-azar patients after chemotherapy. Infection and Immunity 67, 66636669.Google Scholar
Anderson, C. F., Mendez, S. and Sacks, D. L. (2005). Nonhealing infection despite Th1 polarization produced by a strain of Leishmania major in C57BL/6 mice. Journal of Immunology 174, 29342941.Google Scholar
Anderson, C. F., Oukka, M., Kuchroo, V. J. and Sacks, D. (2007). CD4+CD25−Foxp3− Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. Journal of Experimental Medicine 204, 285297. doi: 10.1084/jem.20061886.CrossRefGoogle Scholar
Antinori, S., Cascio, A., Parravicini, C., Bianchi, R. and Corbellino, M. (2008). Leishmaniasis among organ transplant recipients. Lancet Infectious Diseases 8, 191199. doi: 10.1016/S1473-3099(08)70043-4.Google Scholar
Arendse, B., Van Snick, J. and Brombacher, F. (2005). IL-9 is a susceptibility factor in Leishmania major infection by promoting detrimental Th2/type 2 responses. Journal of Immunology 174, 22052211.Google Scholar
Artis, D., Johnson, L. M., Joyce, K., Saris, C., Villarino, A., Hunter, C. A. and Scott, P. (2004). Cutting edge: early IL-4 production governs the requirement for IL-27-WSX-1 signaling in the development of protective Th1 cytokine responses following Leishmania major infection. Journal of Immunology 172, 46724675.Google Scholar
Ato, M., Stager, S., Engwerda, C. R. and Kaye, P. M. (2002). Defective CCR7 expression on dendritic cells contributes to the development of visceral leishmaniasis. Nature Immunology 3, 11851191. doi: 10.1038/ni861.Google Scholar
Ato, M., Maroof, A., Zubairi, S., Nakano, H., Kakiuchi, T. and Kaye, P. M. (2006). Loss of dendritic cell migration and impaired resistance to Leishmania donovani infection in mice deficient in CCL19 and CCL21. Journal of Immunology 176, 54865493.Google Scholar
Bacellar, O., Faria, D., Nascimento, M., Cardoso, T. M., Gollob, K. J., Dutra, W. O., Scott, P. and Carvalho, E. M. (2009). Interleukin 17 production among patients with American cutaneous leishmaniasis. Journal of Infectious Diseases 200, 7578. doi: 10.1086/599380.Google Scholar
Badaro, R. and Johnson, W. D. Jr. (1993). The role of interferon-gamma in the treatment of visceral and diffuse cutaneous leishmaniasis. Journal of Infectious Diseases 167 (Suppl. 1), S13S17.Google Scholar
Bajenoff, M., Breart, B., Huang, A. Y., Qi, H., Cazareth, J., Braud, V. M., Germain, R. N. and Glaichenhaus, N. (2006). Natural killer cell behavior in lymph nodes revealed by static and real-time imaging. Journal of Experimental Medicine 203, 619631.Google Scholar
Banchereau, J. and Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature 392, 245252. doi: 10.1038/32588.CrossRefGoogle ScholarPubMed
Bankoti, R., Gupta, K., Levchenko, A. and Stager, S. (2012). Marginal zone B cells regulate antigen-specific T cell responses during infection. Journal of Immunology 188, 39613971. doi: 10.4049/jimmunol.1102880.Google Scholar
Barral-Netto, M., Barral, A., Brownell, C. E., Skeiky, Y. A., Ellingsworth, L. R., Twardzik, D. R. and Reed, S. G. (1992). Transforming growth factor-beta in leishmanial infection: a parasite escape mechanism. Science 257, 545548.Google Scholar
Basu, M. K. and Ray, M. (2005). Macrophage and Leishmania: an unacceptable coexistence. Critical Reviews in Microbiology 31, 145154. doi: 10.1080/10408410591005101.Google Scholar
Beattie, L., Peltan, A., Maroof, A., Kirby, A., Brown, N., Coles, M., Smith, D. F. and Kaye, P. M. (2010 a). Dynamic imaging of experimental Leishmania donovani-induced hepatic granulomas detects Kupffer cell-restricted antigen presentation to antigen-specific CD8T cells. PLOS Pathogens 6, e1000805. doi: 10.1371/journal.ppat.1000805.CrossRefGoogle Scholar
Beattie, L., Svensson, M., Bune, A., Brown, N., Maroof, A., Zubairi, S., Smith, K. R. and Kaye, P. M. (2010 b). Leishmania donovani-induced expression of signal regulatory protein alpha on Kupffer cells enhances hepatic invariant NKT-cell activation. European Journal of Immunology 40, 117123. doi: 10.1002/eji.200939863.CrossRefGoogle ScholarPubMed
Belkaid, Y. and Rouse, B. T. (2005). Natural regulatory T cells in infectious disease. Nature Immunology 6, 353360. doi: 10.1038/ni1181.Google Scholar
Belkaid, Y., Butcher, B. and Sacks, D. L. (1998). Analysis of cytokine production by inflammatory mouse macrophages at the single-cell level: selective impairment of IL-12 induction in Leishmania-infected cells. European Journal of Immunology 28, 13891400.Google Scholar
Belkaid, Y., Mendez, S., Lira, R., Kadambi, N., Milon, G. and Sacks, D. (2000). A natural model of Leishmania major infection reveals a prolonged “silent” phase of parasite amplification in the skin before the onset of lesion formation and immunity. Journal of Immunology 165, 969977.CrossRefGoogle ScholarPubMed
Belkaid, Y., Hoffmann, K. F., Mendez, S., Kamhawi, S., Udey, M. C., Wynn, T. A. and Sacks, D. L. (2001). The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure. Journal of Experimental Medicine 194, 14971506.CrossRefGoogle ScholarPubMed
Belkaid, Y., Piccirillo, C. A., Mendez, S., Shevach, E. M. and Sacks, D. L. (2002 a). CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420, 502507.CrossRefGoogle ScholarPubMed
Belkaid, Y., Von Stebut, E., Mendez, S., Lira, R., Caler, E., Bertholet, S., Udey, M. C. and Sacks, D. (2002 b). CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. Journal of Immunology 168, 39924000.Google Scholar
Bennett, C. L., Misslitz, A., Colledge, L., Aebischer, T. and Blackburn, C. C. (2001). Silent infection of bone marrow-derived dendritic cells by Leishmania mexicana amastigotes. European Journal of Immunology 31, 876883.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Bern, C., Maguire, J. H. and Alvar, J. (2008). Complexities of assessing the disease burden attributable to leishmaniasis. PLOS Neglected Tropical Diseases 2, e313.Google Scholar
Bertholet, S., Goldszmid, R., Morrot, A., Debrabant, A., Afrin, F., Collazo-Custodio, C., Houde, M., Desjardins, M., Sher, A. and Sacks, D. (2006). Leishmania antigens are presented to CD8+ T cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo. Journal of Immunology 177, 35253533.Google Scholar
Bhattacharyya, S., Ghosh, S., Jhonson, P. L., Bhattacharya, S. K. and Majumdar, S. (2001). Immunomodulatory role of interleukin-10 in visceral leishmaniasis: defective activation of protein kinase C-mediated signal transduction events. Infection and Immunity 69, 14991507. doi: 10.1128/IAI.69.3.1499-1507.2001.Google Scholar
Biedermann, T., Zimmermann, S., Himmelrich, H., Gumy, A., Egeter, O., Sakrauski, A. K., Seegmuller, I., Voigt, H., Launois, P., Levine, A. D., Wagner, H., Heeg, K., Louis, J. A. and Rocken, M. (2001). IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice. Nature Immunology 2, 10541060.Google Scholar
Blackwell, J. M., Barton, C. H., White, J. K., Searle, S., Baker, A. M., Williams, H. and Shaw, M. A. (1995). Genomic organization and sequence of the human NRAMP gene: identification and mapping of a promoter region polymorphism. Molecular Medicine 1, 194205.Google Scholar
Blackwell, J. M., Goswami, T., Evans, C. A., Sibthorpe, D., Papo, N., White, J. K., Searle, S., Miller, E. N., Peacock, C. S., Mohammed, H. and Ibrahim, M. (2001). SLC11A1 (formerly NRAMP1) and disease resistance. Cellular Microbiology 3, 773784.CrossRefGoogle ScholarPubMed
Bogdan, C., Moll, H., Solbach, W. and Rollinghoff, M. (1990). Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes. European Journal of Immunology 20, 11311135. doi: 10.1002/eji.1830200528.CrossRefGoogle Scholar
Bogdan, C., Vodovotz, Y. and Nathan, C. (1991). Macrophage deactivation by interleukin 10. Journal of Experimental Medicine 174, 15491555.Google Scholar
Bogdan, C., Rollinghoff, M. and Diefenbach, A. (2000). The role of nitric oxide in innate immunity. Immunological Reviews 173, 1726.CrossRefGoogle ScholarPubMed
Bohme, M. W., Evans, D. A., Miles, M. A. and Holborow, E. J. (1986). Occurrence of autoantibodies to intermediate filament proteins in human visceral leishmaniasis and their induction by experimental polyclonal B-cell activation. Immunology 59, 583588.Google Scholar
Boulay, J. L., O'Shea, J. J. and Paul, W. E. (2003). Molecular phylogeny within type I cytokines and their cognate receptors. Immunity 19, 159163.Google Scholar
Bourreau, E., Ronet, C., Darcissac, E., Lise, M. C., Sainte Marie, D., Clity, E., Tacchini-Cottier, F., Couppie, P. and Launois, P. (2009). Intralesional regulatory T-cell suppressive function during human acute and chronic cutaneous leishmaniasis due to Leishmania guyanensis. Infection and Immunity 77, 14651474. doi: 10.1128/IAI.01398-08.Google Scholar
Brombacher, F. (2000). The role of interleukin-13 in infectious diseases and allergy. Bioessays 22, 646656.Google Scholar
Brown, D. R. and Reiner, S. L. (1999). Polarized helper-T-cell responses against Leishmania major in the absence of B cells. Infection and Immunity 67, 266270.Google Scholar
Campanelli, A. P., Roselino, A. M., Cavassani, K. A., Pereira, M. S., Mortara, R. A., Brodskyn, C. I., Goncalves, H. S., Belkaid, Y., Barral-Netto, M., Barral, A. and Silva, J. S. (2006). CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells. Journal of Infectious Diseases 193, 13131322. doi: 10.1086/502980.Google Scholar
Carrera, L., Gazzinelli, R. T., Badolato, R., Hieny, S., Muller, W., Kuhn, R. and Sacks, D. L. (1996). Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice. Journal of Experimental Medicine 183, 515526.Google Scholar
Cervia, J. S., Rosen, H. and Murray, H. W. (1993). Effector role of blood monocytes in experimental visceral leishmaniasis. Infection and Immunity 61, 13301333.CrossRefGoogle ScholarPubMed
Chen, Q., Ghilardi, N., Wang, H., Baker, T., Xie, M. H., Gurney, A., Grewal, I. S. and de Sauvage, F. J. (2000). Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 407, 916920. doi: 10.1038/35038103.Google Scholar
Cotterell, S. E., Engwerda, C. R. and Kaye, P. M. (1999). Leishmania donovani infection initiates T cell-independent chemokine responses, which are subsequently amplified in a T cell-dependent manner. European Journal of Immunology 29, 203214.3.0.CO;2-B>CrossRefGoogle Scholar
Dalton, J. E., Maroof, A., Owens, B. M., Narang, P., Johnson, K., Brown, N., Rosenquist, L., Beattie, L., Coles, M. and Kaye, P. M. (2010). Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice. Journal of Clinical Investigation 120, 12041216. doi: 10.1172/JCI41281.Google Scholar
Darrah, P. A., Patel, D. T., De Luca, P. M., Lindsay, R. W., Davey, D. F., Flynn, B. J., Hoff, S. T., Andersen, P., Reed, S. G., Morris, S. L., Roederer, M. and Seder, R. A. (2007). Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nature Medicine 13, 843850. doi: 10.1038/nm1592.Google Scholar
Darrah, P. A., Hegde, S. T., Patel, D. T., Lindsay, R. W., Chen, L., Roederer, M. and Seder, R. A. (2010). IL-10 production differentially influences the magnitude, quality, and protective capacity of Th1 responses depending on the vaccine platform. Journal of Experimental Medicine 207, 14211433. doi: 10.1084/jem.20092532.Google Scholar
da Silva Santos, S., Boaventura, V., Ribeiro Cardoso, C., Tavares, N., Lordelo, M. J., Noronha, A., Costa, J., Borges, V. M., de Oliveira, C. I., Van Weyenbergh, J., Barral, A., Barral-Netto, M. and Brodskyn, C. I. (2013). CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNgamma(+)-mediated parasite killing in human cutaneous leishmaniasis. Journal of Investigative Dermatology 133, 15331540. doi: 10.1038/jid.2013.4.Google Scholar
Deak, E., Jayakumar, A., Cho, K. W., Goldsmith-Pestana, K., Dondji, B., Lambris, J. D. and McMahon-Pratt, D. (2010). Murine visceral leishmaniasis: IgM and polyclonal B-cell activation lead to disease exacerbation. European Journal of Immunology 40, 13551368. doi: 10.1002/eji.200939455.Google Scholar
Demoulin, J. B. and Renauld, J. C. (1998). Interleukin 9 and its receptor: an overview of structure and function. International Reviews of Immunology 16, 345364.Google Scholar
Dey, R., Majumder, N., Bhattacharyya Majumdar, S., Bhattacharjee, S., Banerjee, S., Roy, S. and Majumdar, S. (2007). Induction of host protective Th1 immune response by chemokines in Leishmania donovani-infected BALB/c mice. Scandinavian Journal of Immunology 66, 671683. doi: 10.1111/j.1365-3083.2007.02025.x.CrossRefGoogle ScholarPubMed
Diefenbach, A., Schindler, H., Donhauser, N., Lorenz, E., Laskay, T., MacMicking, J., Rollinghoff, M., Gresser, I. and Bogdan, C. (1998). Type 1 interferon (IFNalpha/beta) and type 2 nitric oxide synthase regulate the innate immune response to a protozoan parasite. Immunity 8, 7787.Google Scholar
Ehrchen, J. M., Roebrock, K., Foell, D., Nippe, N., von Stebut, E., Weiss, J. M., Munck, N. A., Viemann, D., Varga, G., Muller-Tidow, C., Schuberth, H. J., Roth, J. and Sunderkotter, C. (2010). Keratinocytes determine Th1 immunity during early experimental leishmaniasis. PLOS Pathogens 6, e1000871. doi: 10.1371/journal.ppat.1000871.Google Scholar
Engwerda, C. R. and Kaye, P. M. (2000). Organ-specific immune responses associated with infectious disease. Immunology Today 21, 7378. doi: 10.1016/S0167-5699(99)01549-2.Google Scholar
Engwerda, C. R., Smelt, S. C. and Kaye, P. M. (1996). An in vivo analysis of cytokine production during Leishmania donovani infection in scid mice. Experimental Parasitology 84, 195202. doi: 10.1006/expr.1996.0105.CrossRefGoogle Scholar
Engwerda, C. R., Murphy, M. L., Cotterell, S. E., Smelt, S. C. and Kaye, P. M. (1998). Neutralization of IL-12 demonstrates the existence of discrete organ-specific phases in the control of Leishmania donovani. European Journal of Immunology 28, 669680.Google Scholar
Engwerda, C. R., Ato, M., Cotterell, S. E., Mynott, T. L., Tschannerl, A., Gorak-Stolinska, P. M. and Kaye, P. M. (2002). A role for tumor necrosis factor-alpha in remodeling the splenic marginal zone during Leishmania donovani infection. American Journal of Pathology 161, 429437.Google Scholar
Engwerda, C. R., Ato, M., Stager, S., Alexander, C. E., Stanley, A. C. and Kaye, P. M. (2004). Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of Leishmania donovani infection. American Journal of Pathology 165, 21232133.Google Scholar
Faria, D. R., Souza, P. E., Duraes, F. V., Carvalho, E. M., Gollob, K. J., Machado, P. R. and Dutra, W. O. (2009). Recruitment of CD8(+) T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis. Parasite Immunology 31, 432439. doi: 10.1111/j.1365-3024.2009.01125.x.Google Scholar
Flohe, S., Lang, T. and Moll, H. (1997). Synthesis, stability, and subcellular distribution of major histocompatibility complex class II molecules in Langerhans cells infected with Leishmania major. Infection and Immunity 65, 34443450.Google Scholar
Galvao-Castro, B., Sa Ferreira, J. A., Marzochi, K. F., Marzochi, M. C., Coutinho, S. G. and Lambert, P. H. (1984). Polyclonal B cell activation, circulating immune complexes and autoimmunity in human American visceral leishmaniasis. Clinical and Experimental Immunology 56, 5866.Google Scholar
Gautam, S., Kumar, R., Singh, N., Singh, A. K., Rai, M., Sacks, D., Sundar, S. and Nylen, S. (2014). CD8T cell exhaustion in human visceral leishmaniasis. Journal of Infectious Diseases 209, 290299. doi: 10.1093/infdis/jit401.Google Scholar
Gessner, A., Blum, H. and Rollinghoff, M. (1993 a). Differential regulation of IL-9-expression after infection with Leishmania major in susceptible and resistant mice. Immunobiology 189, 419435.Google Scholar
Gessner, A., Vieth, M., Will, A., Schroppel, K. and Rollinghoff, M. (1993 b). Interleukin-7 enhances antimicrobial activity against Leishmania major in murine macrophages. Infection and Immunity 61, 40084012.CrossRefGoogle ScholarPubMed
Ghalib, H. W., Piuvezam, M. R., Skeiky, Y. A., Siddig, M., Hashim, F. A., el-Hassan, A. M., Russo, D. M. and Reed, S. G. (1993). Interleukin 10 production correlates with pathology in human Leishmania donovani infections. Journal of Clinical Investigation 92, 324329. doi: 10.1172/JCI116570.Google Scholar
Ghalib, H. W., Whittle, J. A., Kubin, M., Hashim, F. A., el-Hassan, A. M., Grabstein, K. H., Trinchieri, G. and Reed, S. G. (1995). IL-12 enhances Th1-type responses in human Leishmania donovani infections. Journal of Immunology 154, 46234629.Google Scholar
Ghose, A. C., Haldar, J. P., Pal, S. C., Mishra, B. P. and Mishra, K. K. (1980). Serological investigations on Indian kala-azar. Clinical and Experimental Immunology 40, 318326.Google Scholar
Gollob, K. J., Antonelli, L. R., Faria, D. R., Keesen, T. S. and Dutra, W. O. (2008). Immunoregulatory mechanisms and CD4-CD8- (double negative) T cell subpopulations in human cutaneous leishmaniasis: a balancing act between protection and pathology. International Immunopharmacology 8, 13381343. doi: 10.1016/j.intimp.2008.03.016.Google Scholar
Gonzalez-Lombana, C., Gimblet, C., Bacellar, O., Oliveira, W. W., Passos, S., Carvalho, L. P., Goldschmidt, M., Carvalho, E. M. and Scott, P. (2013). IL-17 mediates immunopathology in the absence of IL-10 following Leishmania major infection. PLOS Pathogens 9, e1003243. doi: 10.1371/journal.ppat.1003243.Google Scholar
Gorak, P. M., Engwerda, C. R. and Kaye, P. M. (1998). Dendritic cells, but not macrophages, produce IL-12 immediately following Leishmania donovani infection. European Journal of Immunology 28, 687695.Google Scholar
Goswami, T., Bhattacharjee, A., Babal, P., Searle, S., Moore, E., Li, M. and Blackwell, J. M. (2001). Natural-resistance-associated macrophage protein 1 is an H+/bivalent cation antiporter. Biochemical Journal 354, 511519.CrossRefGoogle Scholar
Groux, H., Cottrez, F., Rouleau, M., Mauze, S., Antonenko, S., Hurst, S., McNeil, T., Bigler, M., Roncarolo, M. G. and Coffman, R. L. (1999). A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. Journal of Immunology 162, 17231729.CrossRefGoogle ScholarPubMed
Guimaraes-Costa, A. B., Nascimento, M. T., Froment, G. S., Soares, R. P., Morgado, F. N., Conceicao-Silva, F. and Saraiva, E. M. (2009). Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps. Proceedings of the National Academy of Sciences USA 106, 67486753. doi: 10.1073/pnas.0900226106.CrossRefGoogle ScholarPubMed
Gupta, G., Bhattacharjee, S., Bhattacharyya, S., Bhattacharya, P., Adhikari, A., Mukherjee, A., Bhattacharyya Majumdar, S. and Majumdar, S. (2009). CXC chemokine-mediated protection against visceral leishmaniasis: involvement of the proinflammatory response. Journal of Infectious Diseases 200, 13001310. doi: 10.1086/605895.Google Scholar
Handman, E. (1999). Cell biology of Leishmania. Advances in Parasitology 44, 139.Google Scholar
Havell, E. A. (1989). Evidence that tumor necrosis factor has an important role in antibacterial resistance. Journal of Immunology 143, 28942899.CrossRefGoogle ScholarPubMed
Heinzel, F. P., Rerko, R. M., Hatam, F. and Locksley, R. M. (1993). IL-2 is necessary for the progression of leishmaniasis in susceptible murine hosts. Journal of Immunology 150, 39243931.Google Scholar
Himmelrich, H., Launois, P., Maillard, I., Biedermann, T., Tacchini-Cottier, F., Locksley, R. M., Rocken, M. and Louis, J. A. (2000). In BALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease. Journal of Immunology 164, 48194825.Google Scholar
Hoerauf, A., Solbach, W., Rollinghoff, M. and Gessner, A. (1995). Effect of IL-7 treatment on Leishmania major-infected BALB.Xid mice: enhanced lymphopoiesis with sustained lack of B1 cells and clinical aggravation of disease. International Immunology 7, 18791884.Google Scholar
Houde, M., Bertholet, S., Gagnon, E., Brunet, S., Goyette, G., Laplante, A., Princiotta, M. F., Thibault, P., Sacks, D. and Desjardins, M. (2003). Phagosomes are competent organelles for antigen cross-presentation. Nature 425, 402406.Google Scholar
Huber, M., Timms, E., Mak, T. W., Rollinghoff, M. and Lohoff, M. (1998). Effective and long-lasting immunity against the parasite Leishmania major in CD8-deficient mice. Infection and Immunity 66, 39683970.Google Scholar
Iezzi, G., Karjalainen, K. and Lanzavecchia, A. (1998). The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8, 8995. doi: 10.1016/S1074-7613(00)80461-6.Google Scholar
Iniesta, V., Gomez-Nieto, L. C. and Corraliza, I. (2001). The inhibition of arginase by N(omega)-hydroxy-l-arginine controls the growth of Leishmania inside macrophages. Journal of Experimental Medicine 193, 777784.Google Scholar
Joshi, T., Rodriguez, S., Perovic, V., Cockburn, I. A. and Stager, S. (2009). B7-H1 blockade increases survival of dysfunctional CD8(+) T cells and confers protection against Leishmania donovani infections. PLOS Pathogens 5, e1000431. doi: 10.1371/journal.ppat.1000431.Google Scholar
Kane, M. M. and Mosser, D. M. (2001). The role of IL-10 in promoting disease progression in leishmaniasis. Journal of Immunology 166, 11411147.Google Scholar
Karplus, T. M., Jeronimo, S. M., Chang, H., Helms, B. K., Burns, T. L., Murray, J. C., Mitchell, A. A., Pugh, E. W., Braz, R. F., Bezerra, F. L. and Wilson, M. E. (2002). Association between the tumor necrosis factor locus and the clinical outcome of Leishmania chagasi infection. Infection and Immunity 70, 69196925.Google Scholar
Kaye, P. M. and Bancroft, G. J. (1992). Leishmania donovani infection in scid mice: lack of tissue response and in vivo macrophage activation correlates with failure to trigger natural killer cell-derived gamma interferon production in vitro. Infection and Immunity 60, 43354342.Google Scholar
Kedzierski, L., Curtis, J. M., Doherty, P. C., Handman, E. and Kedzierska, K. (2008). Decreased IL-10 and IL-13 production and increased CD44hi T cell recruitment contribute to Leishmania major immunity induced by non-persistent parasites. European Journal of Immunology 38, 30903100. doi: 10.1002/eji.200838423.Google Scholar
Kedzierski, L., Zhu, Y. and Handman, E. (2006). Leishmania vaccines: progress and problems. Parasitology 133 (Suppl.), S87S112.Google Scholar
Kedzierski, L., Sakthianandeswaren, A., Curtis, J. M., Andrews, P. C., Junk, P. C. and Kedzierska, K. (2009). Leishmaniasis: current treatment and prospects for new drugs and vaccines. Current Medicinal Chemistry 16, 599614.Google Scholar
Khalil, E. A., Ayed, N. B., Musa, A. M., Ibrahim, M. E., Mukhtar, M. M., Zijlstra, E. E., Elhassan, I. M., Smith, P. G., Kieny, P. M., Ghalib, H. W., Zicker, F., Modabber, F. and Elhassan, A. M. (2005). Dichotomy of protective cellular immune responses to human visceral leishmaniasis. Clinical and Experimental Immunology 140, 349353.Google Scholar
Kirkpatrick, C. E., Farrell, J. P., Warner, J. F. and Denner, G. (1985). Participation of natural killer cells in the recovery of mice from visceral leishmaniasis. Cellular Immunology 92, 163171.CrossRefGoogle ScholarPubMed
Kopf, M., Le Gros, G., Bachmann, M., Lamers, M. C., Bluethmann, H. and Kohler, G. (1993). Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 362, 245248.CrossRefGoogle ScholarPubMed
Kopf, M., Brombacher, F., Kohler, G., Kienzle, G., Widmann, K. H., Lefrang, K., Humborg, C., Ledermann, B. and Solbach, W. (1996). IL-4-deficient Balb/c mice resist infection with Leishmania major. Journal of Experimental Medicine 184, 11271136.Google Scholar
Kurkjian, K. M., Mahmutovic, A. J., Kellar, K. L., Haque, R., Bern, C. and Secor, W. E. (2006). Multiplex analysis of circulating cytokines in the sera of patients with different clinical forms of visceral leishmaniasis. Cytometry A 69, 353358. doi: 10.1002/cyto.a.20256.Google Scholar
Lachaud, L., Bourgeois, N., Plourde, M., Leprohon, P., Bastien, P. and Ouellette, M. (2009). Parasite susceptibility to amphotericin B in failures of treatment for visceral leishmaniasis in patients coinfected with HIV type 1 and Leishmania infantum. Clinical Infectious Diseases 48, e16e22. doi: 10.1086/595710.Google Scholar
Langrish, C. L., McKenzie, B. S., Wilson, N. J., de Waal Malefyt, R., Kastelein, R. A. and Cua, D. J. (2004). IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunological Reviews 202, 96105. doi: 10.1111/j.0105-2896.2004.00214.x.Google Scholar
Lazarski, C. A., Ford, J., Katzman, S. D., Rosenberg, A. F. and Fowell, D. J. (2013). IL-4 attenuates Th1-associated chemokine expression and Th1 trafficking to inflamed tissues and limits pathogen clearance. PLOS ONE 8, e71949. doi: 10.1371/journal.pone.0071949.Google Scholar
Leclercq, V., Lebastard, M., Belkaid, Y., Louis, J. and Milon, G. (1996). The outcome of the parasitic process initiated by Leishmania infantum in laboratory mice: a tissue-dependent pattern controlled by the Lsh and MHC loci. Journal of Immunology 157, 45374545.CrossRefGoogle ScholarPubMed
Li, J., Hunter, C. A. and Farrell, J. P. (1999). Anti-TGF-beta treatment promotes rapid healing of Leishmania major infection in mice by enhancing in vivo nitric oxide production. Journal of Immunology 162, 974979.Google Scholar
Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A. K. and Flavell, R. A. (2006). Transforming growth factor-beta regulation of immune responses. Annual Review of Immunology 24, 99146. doi: 10.1146/annurev.immunol.24.021605.090737.Google Scholar
Liese, J., Schleicher, U. and Bogdan, C. (2008). The innate immune response against Leishmania parasites. Immunobiology 213, 377387. doi: 10.1016/j.imbio.2007.12.005.Google Scholar
Liew, F. Y., Li, Y. and Millott, S. (1990). Tumor necrosis factor-alpha synergizes with IFN-gamma in mediating killing of Leishmania major through the induction of nitric oxide. Journal of Immunology 145, 43064310.Google Scholar
Maroof, A., Beattie, L., Zubairi, S., Svensson, M., Stager, S. and Kaye, P. M. (2008). Posttranscriptional regulation of II10 gene expression allows natural killer cells to express immunoregulatory function. Immunity 29, 295305. doi: 10.1016/j.immuni.2008.06.012.Google Scholar
Maroof, A., Brown, N., Smith, B., Hodgkinson, M. R., Maxwell, A., Losch, F. O., Fritz, U., Walden, P., Lacey, C. N., Smith, D. F., Aebischer, T. and Kaye, P. M. (2012). Therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis. Journal of Infectious Diseases 205, 853863. doi: 10.1093/infdis/jir842.Google Scholar
Mary, C., Auriault, V., Faugere, B. and Dessein, A. J. (1999). Control of Leishmania infantum infection is associated with CD8(+) and gamma interferon- and interleukin-5-producing CD4(+) antigen-specific T cells. Infection and Immunity 67, 55595566.Google Scholar
Matheoud, D., Moradin, N., Bellemare-Pelletier, A., Shio, M. T., Hong, W. J., Olivier, M., Gagnon, E., Desjardins, M. and Descoteaux, A. (2013). Leishmania evades host immunity by inhibiting antigen cross-presentation through direct cleavage of the SNARE VAMP8. Cell Host Microbe 14, 1525. doi: 10.1016/j.chom.2013.06.003.Google Scholar
Matthews, D. J., Emson, C. L., McKenzie, G. J., Jolin, H. E., Blackwell, J. M. and McKenzie, A. N. (2000). IL-13 is a susceptibility factor for Leishmania major infection. Journal of Immunology 164, 14581462.Google Scholar
Mattner, F., Magram, J., Ferrante, J., Launois, P., Di Padova, K., Behin, R., Gately, M. K., Louis, J. A. and Alber, G. (1996). Genetically resistant mice lacking interleukin-12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response. European Journal of Immunology 26, 15531559.Google Scholar
Maurer, M., Lopez Kostka, S., Siebenhaar, F., Moelle, K., Metz, M., Knop, J. and von Stebut, E. (2006). Skin mast cells control T cell-dependent host defense in Leishmania major infections. FASEB Journal 20, 24602467.Google Scholar
McElrath, M. J., Murray, H. W. and Cohn, Z. A. (1988). The dynamics of granuloma formation in experimental visceral leishmaniasis. Journal of Experimental Medicine 167, 19271937.Google Scholar
McFarlane, E., Perez, C., Charmoy, M., Allenbach, C., Carter, K. C., Alexander, J. and Tacchini-Cottier, F. (2008). Neutrophils contribute to development of a protective immune response during onset of infection with Leishmania donovani. Infection and Immunity 76, 532541.Google Scholar
Miralles, G. D., Stoeckle, M. Y., McDermott, D. F., Finkelman, F. D. and Murray, H. W. (1994). Th1 and Th2 cell-associated cytokines in experimental visceral leishmaniasis. Infection and Immunity 62, 10581063.Google Scholar
Modabber, F. (2010). Leishmaniasis vaccines: past, present and future. International Journal of Antimicrobial Agents 36 (Suppl. 1), S58S61. doi: 10.1016/j.ijantimicag.2010.06.024.Google Scholar
Monteyne, P., Renauld, J. C., Van Broeck, J., Dunne, D. W., Brombacher, F. and Coutelier, J. P. (1997). IL-4-independent regulation of in vivo IL-9 expression. Journal of Immunology 159, 26162623.Google Scholar
Moore, J. W., Beattie, L., Dalton, J. E., Owens, B. M., Maroof, A., Coles, M. C. and Kaye, P. M. (2012). B cell: T cell interactions occur within hepatic granulomas during experimental visceral leishmaniasis. PLOS ONE 7, e34143. doi: 10.1371/journal.pone.0034143.Google Scholar
Moore, K. W., de Waal Malefyt, R., Coffman, R. L. and O'Garra, A. (2001). Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology 19, 683765. doi: 10.1146/annurev.immunol.19.1.683.Google Scholar
Mougneau, E., Bihl, F. and Glaichenhaus, N. (2011). Cell biology and immunology of Leishmania. Immunological Reviews 240, 286296. doi: 10.1111/j.1600-065X.2010.00983.x.Google Scholar
Mukbel, R. M., Patten, C. Jr., Gibson, K., Ghosh, M., Petersen, C. and Jones, D. E. (2007). Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide. American Journal of Tropical Medicine and Hygiene 76, 669675.Google Scholar
Muller, I., Kropf, P., Etges, R. J. and Louis, J. A. (1993). Gamma interferon response in secondary Leishmania major infection: role of CD8+ T cells. Infection and Immunity 61, 37303738.CrossRefGoogle ScholarPubMed
Murphy, M. L., Wille, U., Villegas, E. N., Hunter, C. A. and Farrell, J. P. (2001). IL-10 mediates susceptibility to Leishmania donovani infection. European Journal of Immunology 31, 28482856.Google Scholar
Murray, H. W. (1990). Effect of continuous administration of interferon-gamma in experimental visceral leishmaniasis. Journal of Infectious Diseases 161, 992994.Google Scholar
Murray, H. W. (1997). Endogenous interleukin-12 regulates acquired resistance in experimental visceral leishmaniasis. Journal of Infectious Diseases 175, 14771479.CrossRefGoogle ScholarPubMed
Murray, H. W. (2001). Tissue granuloma structure-function in experimental visceral leishmaniasis. International Journal of Experimental Pathology 82, 249267.CrossRefGoogle ScholarPubMed
Murray, H. W. (2008). Accelerated control of visceral Leishmania donovani infection in interleukin-6-deficient mice. Infection and Immunity 76, 40884091. doi: 10.1128/IAI.00490-08.Google Scholar
Murray, H. W. and Cartelli, D. M. (1983). Killing of intracellular Leishmania donovani by human mononuclear phagocytes. Evidence for oxygen-dependent and -independent leishmanicidal activity. Journal of Clinical Investigation 72, 3244.Google Scholar
Murray, H. W. and Nathan, C. F. (1999). Macrophage microbicidal mechanisms in vivo: reactive nitrogen versus oxygen intermediates in the killing of intracellular visceral Leishmania donovani. Journal of Experimental Medicine 189, 741746.Google Scholar
Murray, H. W., Stern, J. J., Welte, K., Rubin, B. Y., Carriero, S. M. and Nathan, C. F. (1987). Experimental visceral leishmaniasis: production of interleukin 2 and interferon-gamma, tissue immune reaction, and response to treatment with interleukin 2 and interferon-gamma. Journal of Immunology 138, 22902297.Google Scholar
Murray, H. W., Squires, K. E., Miralles, C. D., Stoeckle, M. Y., Granger, A. M., Granelli-Piperno, A. and Bogdan, C. (1992). Acquired resistance and granuloma formation in experimental visceral leishmaniasis. Differential T cell and lymphokine roles in initial versus established immunity. Journal of Immunology 148, 18581863.Google Scholar
Murray, H. W., Miralles, G. D., Stoeckle, M. Y. and McDermott, D. F. (1993). Role and effect of IL-2 in experimental visceral leishmaniasis. Journal of Immunology 151, 929938.Google Scholar
Murray, H. W., Cervia, J. S., Hariprashad, J., Taylor, A. P., Stoeckle, M. Y. and Hockman, H. (1995 a). Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis. Journal of Clinical Investigation 95, 11831192. doi: 10.1172/JCI117767.Google Scholar
Murray, H. W., Hariprashad, J., Aguero, B., Arakawa, T. and Yeganegi, H. (1995 b). Antimicrobial response of a T cell-deficient host to cytokine therapy: effect of interferon-gamma in experimental visceral leishmaniasis in nude mice. Journal of Infectious Diseases 171, 13091316.Google Scholar
Murray, H. W., Jungbluth, A., Ritter, E., Montelibano, C. and Marino, M. W. (2000). Visceral leishmaniasis in mice devoid of tumor necrosis factor and response to treatment. Infection and Immunity 68, 62896293.Google Scholar
Murray, H. W., Moreira, A. L., Lu, C. M., DeVecchio, J. L., Matsuhashi, M., Ma, X. and Heinzel, F. P. (2003). Determinants of response to interleukin-10 receptor blockade immunotherapy in experimental visceral leishmaniasis. Journal of Infectious Diseases 188, 458464. doi: 10.1086/376510.Google Scholar
Nacy, C. A., Meierovics, A. I., Belosevic, M. and Green, S. J. (1991). Tumor necrosis factor-alpha: central regulatory cytokine in the induction of macrophage antimicrobial activities. Pathobiology 59, 182184.Google Scholar
Nashed, B. F., Maekawa, Y., Takashima, M., Zhang, T., Ishii, K., Dainichi, T., Ishikawa, H., Sakai, T., Hisaeda, H. and Himeno, K. (2000). Different cytokines are required for induction and maintenance of the Th2 type response in DBA/2 mice resistant to infection with Leishmania major. Microbes and Infection 2, 14351443. doi: 10.1016/S1286-4579(00)01298-3.Google Scholar
Ng, L. G., Hsu, A., Mandell, M. A., Roediger, B., Hoeller, C., Mrass, P., Iparraguirre, A., Cavanagh, L. L., Triccas, J. A., Beverley, S. M., Scott, P. and Weninger, W. (2008). Migratory dermal dendritic cells act as rapid sensors of protozoan parasites. PLOS Pathogens 4, e1000222. doi: 10.1371/journal.ppat.1000222.Google Scholar
Noben-Trauth, N., Kropf, P. and Muller, I. (1996). Susceptibility to Leishmania major infection in interleukin-4-deficient mice. Science 271, 987990.Google Scholar
Nylen, S., Maurya, R., Eidsmo, L., Manandhar, K. D., Sundar, S. and Sacks, D. (2007). Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis. Journal of Experimental Medicine 204, 805817. doi: 10.1084/jem.20061141.Google Scholar
O'Garra, A. (1998). Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8, 275283. doi: 10.1016/S1074-7613(00)80533-6.Google Scholar
O'Garra, A. and Vieira, P. (2007). T(H)1 cells control themselves by producing interleukin-10. Nature Reviews Immunology 7, 425428. doi: 10.1038/nri2097.Google Scholar
Oghumu, S., Lezama-Davila, C. M., Isaac-Marquez, A. P. and Satoskar, A. R. (2010). Role of chemokines in regulation of immunity against leishmaniasis. Experimental Parasitology 126, 389396. doi: 10.1016/j.exppara.2010.02.010.Google Scholar
Okwor, I., Liu, D., Beverley, S. M. and Uzonna, J. E. (2009). Inoculation of killed Leishmania major into immune mice rapidly disrupts immunity to a secondary challenge via IL-10-mediated process. Proceedings of the National Academy of Sciences USA 106, 1395113956.Google Scholar
Oppmann, B., Lesley, R., Blom, B., Timans, J. C., Xu, Y., Hunte, B., Vega, F., Yu, N., Wang, J., Singh, K., Zonin, F., Vaisberg, E., Churakova, T., Liu, M., Gorman, D., Wagner, J., Zurawski, S., Liu, Y., Abrams, J. S., Moore, K. W., Rennick, D., de Waal-Malefyt, R., Hannum, C., Bazan, J. F. and Kastelein, R. A. (2000). Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13, 715725.Google Scholar
Owens, B. M., Beattie, L., Moore, J. W., Brown, N., Mann, J. L., Dalton, J. E., Maroof, A. and Kaye, P. M. (2012). IL-10-producing Th1 cells and disease progression are regulated by distinct CD11c(+) cell populations during visceral leishmaniasis. PLOS Pathogens 8, e1002827. doi: 10.1371/journal.ppat.1002827.Google Scholar
Padigel, U. M., Alexander, J. and Farrell, J. P. (2003). The role of interleukin-10 in susceptibility of BALB/c mice to infection with Leishmania mexicana and Leishmania amazonensis. Journal of Immunology 171, 37053710.Google Scholar
Pakpour, N., Zaph, C. and Scott, P. (2008). The central memory CD4+ T cell population generated during Leishmania major infection requires IL-12 to produce IFN-gamma. Journal of Immunology 180, 82998305.Google Scholar
Pavli, A. and Maltezou, H. C. (2010). Leishmaniasis, an emerging infection in travelers. International Journal of Infectious Diseases 14, e1032e1039. doi: 10.1016/j.ijid.2010.06.019.Google Scholar
Peters, N. C. and Sacks, D. L. (2009). The impact of vector-mediated neutrophil recruitment on cutaneous leishmaniasis. Cellular Microbiology 11, 12901296.Google Scholar
Peters, N. C., Egen, J. G., Secundino, N., Debrabant, A., Kimblin, N., Kamhawi, S., Lawyer, P., Fay, M. P., Germain, R. N. and Sacks, D. (2008). In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies. Science 321, 970974.Google Scholar
Phillips, R., Svensson, M., Aziz, N., Maroof, A., Brown, N., Beattie, L., Signoret, N. and Kaye, P. M. (2010). Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7. PLOS Pathogens 6, e1000813. doi: 10.1371/journal.ppat.1000813.CrossRefGoogle ScholarPubMed
Polley, R., Zubairi, S. and Kaye, P. M. (2005). The fate of heterologous CD4+ T cells during Leishmania donovani infection. European Journal of Immunology 35, 498504. doi: 10.1002/eji.200425436.Google Scholar
Polley, R., Stager, S., Prickett, S., Maroof, A., Zubairi, S., Smith, D. F. and Kaye, P. M. (2006). Adoptive immunotherapy against experimental visceral leishmaniasis with CD8+ T cells requires the presence of cognate antigen. Infection and Immunity 74, 773776. doi: 10.1128/IAI.74.1.773-776.2006.Google Scholar
Pontes De Carvalho, L. C., Badaro, R., Carvalho, E. M., Lannes-Vieira, J., Vinhaes, L., Orge, G., Marsochi, M. C. and Galvao-Castro, B. (1986). Nature and incidence of erythrocyte-bound IgG and some aspects of the physiopathogenesis of anaemia in American visceral leishmaniasis. Clinical and Experimental Immunology 64, 495502.Google Scholar
Radwanska, M., Cutler, A. J., Hoving, J. C., Magez, S., Holscher, C., Bohms, A., Arendse, B., Kirsch, R., Hunig, T., Alexander, J., Kaye, P. and Brombacher, F. (2007). Deletion of IL-4Ralpha on CD4T cells renders BALB/c mice resistant to Leishmania major infection. PLOS Pathogens 3, e68.Google Scholar
Randolph, G. J. (2001). Dendritic cell migration to lymph nodes: cytokines, chemokines, and lipid mediators. Seminars in Immunology 13, 267274. doi: 10.1006/smim.2001.0322S1044-5323(01)90322-7.Google Scholar
Reiner, S. L. and Locksley, R. M. (1995). The regulation of immunity to Leishmania major. Annual Review of Immunology 13, 151177.Google Scholar
Ricardo-Carter, C., Favila, M., Polando, R. E., Cotton, R. N., Bogard Horner, K., Condon, D., Ballhorn, W., Whitcomb, J. P., Yadav, M., Geister, R. L., Schorey, J. S. and McDowell, M. A. (2013). Leishmania major inhibits IL-12 in macrophages by signalling through CR3 (CD11b/CD18) and down-regulation of ETS-mediated transcription. Parasite Immunology 35, 409420. doi: 10.1111/pim.12049.Google Scholar
Ritter, U., Meissner, A., Scheidig, C. and Korner, H. (2004). CD8 alpha- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis. European Journal of Immunology 34, 15421550. doi: 10.1002/eji.200324586.Google Scholar
Rodriguez, A., Regnault, A., Kleijmeer, M., Ricciardi-Castagnoli, P. and Amigorena, S. (1999). Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nature Cell Biology 1, 362368.Google Scholar
Ronet, C., Voigt, H., Himmelrich, H., Doucey, M. A., Hauyon-La Torre, Y., Revaz-Breton, M., Tacchini-Cottier, F., Bron, C., Louis, J. and Launois, P. (2008). Leishmania major-specific B cells are necessary for Th2 cell development and susceptibility to L. major LV39 in BALB/c mice. Journal of Immunology 180, 48254835.Google Scholar
Ronet, C., Hauyon-La Torre, Y., Revaz-Breton, M., Mastelic, B., Tacchini-Cottier, F., Louis, J. and Launois, P. (2010). Regulatory B cells shape the development of Th2 immune responses in BALB/c mice infected with Leishmania major through IL-10 production. Journal of Immunology 184, 886894. doi: 10.4049/jimmunol.0901114.Google Scholar
Rosas, L. E., Satoskar, A. A., Roth, K. M., Keiser, T. L., Barbi, J., Hunter, C., de Sauvage, F. J. and Satoskar, A. R. (2006). Interleukin-27R (WSX-1/T-cell cytokine receptor) gene-deficient mice display enhanced resistance to Leishmania donovani infection but develop severe liver immunopathology. American Journal of Pathology 168, 158169.Google Scholar
Rostan, O., Gangneux, J. P., Piquet-Pellorce, C., Manuel, C., McKenzie, A. N., Guiguen, C., Samson, M. and Robert-Gangneux, F. (2013). The IL-33/ST2 axis is associated with human visceral leishmaniasis and suppresses Th1 responses in the livers of BALB/c mice infected with Leishmania donovani. mBio 4, e00383–e00313. doi: 10.1128/mBio.00383-13.Google Scholar
Rousseau, D., Demartino, S., Ferrua, B., Michiels, J. F., Anjuere, F., Fragaki, K., Le Fichoux, Y. and Kubar, J. (2001). In vivo involvement of polymorphonuclear neutrophils in Leishmania infantum infection. BMC Microbiology 1, 17.CrossRefGoogle ScholarPubMed
Ruiz, J. H. and Becker, I. (2007). CD8 cytotoxic T cells in cutaneous leishmaniasis. Parasite Immunology 29, 671678.Google Scholar
Sacks, D. and Noben-Trauth, N. (2002). The immunology of susceptibility and resistance to Leishmania major in mice. Nature Reviews Immunology 2, 845858.Google Scholar
Sacks, D. L., Scott, P. A., Asofsky, R. and Sher, F. A. (1984). Cutaneous leishmaniasis in anti-IgM-treated mice: enhanced resistance due to functional depletion of a B cell-dependent T cell involved in the suppressor pathway. Journal of Immunology 132, 20722077.Google Scholar
Sacks, D. L., Lal, S. L., Shrivastava, S. N., Blackwell, J. and Neva, F. A. (1987). An analysis of T cell responsiveness in Indian kala-azar. Journal of Immunology 138, 908913.Google Scholar
Sadick, M. D., Heinzel, F. P., Holaday, B. J., Pu, R. T., Dawkins, R. S. and Locksley, R. M. (1990). Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. Journal of Experimental Medicine 171, 115127.CrossRefGoogle Scholar
Sato, N., Kuziel, W. A., Melby, P. C., Reddick, R. L., Kostecki, V., Zhao, W., Maeda, N., Ahuja, S. K. and Ahuja, S. S. (1999). Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice. Journal of Immunology 163, 55195525.Google Scholar
Satoskar, A. R., Stamm, L. M., Zhang, X., Satoskar, A. A., Okano, M., Terhorst, C., David, J. R. and Wang, B. (1999). Mice lacking NK cells develop an efficient Th1 response and control cutaneous Leishmania major infection. Journal of Immunology 162, 67476754.Google Scholar
Scharton, T. M. and Scott, P. (1993). Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. Journal of Experimental Medicine 178, 567577.Google Scholar
Schwarz, T., Remer, K. A., Nahrendorf, W., Masic, A., Siewe, L., Muller, W., Roers, A. and Moll, H. (2013). T cell-derived IL-10 determines leishmaniasis disease outcome and is suppressed by a dendritic cell based vaccine. PLOS Pathogens 9, e1003476. doi: 10.1371/journal.ppat.1003476.Google Scholar
Scott, P. (1989). The role of TH1 and TH2 cells in experimental cutaneous leishmaniasis. Experimental Parasitology 68, 369372.Google Scholar
Scott, P., Eaton, A., Gause, W. C., di Zhou, X. and Hondowicz, B. (1996). Early IL-4 production does not predict susceptibility to Leishmania major. Experimental Parasitology 84, 178187. doi: 10.1006/expr.1996.0103.Google Scholar
Scott, P., Artis, D., Uzonna, J. and Zaph, C. (2004). The development of effector and memory T cells in cutaneous leishmaniasis: the implications for vaccine development. Immunological Reviews 201, 318338.Google Scholar
Searle, S., Bright, N. A., Roach, T. I., Atkinson, P. G., Barton, C. H., Meloen, R. H. and Blackwell, J. M. (1998). Localisation of Nramp1 in macrophages: modulation with activation and infection. Journal of Cell Science 111, 28552866.Google Scholar
Segal, A. W. (2005). How neutrophils kill microbes. Annual Review of Immunology 23, 197223. doi: 10.1146/annurev.immunol.23.021704.115653.Google Scholar
Silveira, F. T., Lainson, R., Gomes, C. M., Laurenti, M. D. and Corbett, C. E. (2008). Reviewing the role of the dendritic Langerhans cells in the immunopathogenesis of American cutaneous leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 102, 10751080. doi: 10.1016/j.trstmh.2008.05.020.Google Scholar
Silvestre, R., Cordeiro-Da-Silva, A., Santarem, N., Vergnes, B., Sereno, D. and Ouaissi, A. (2007). SIR2-deficient Leishmania infantum induces a defined IFN-gamma/IL-10 pattern that correlates with protection. Journal of Immunology 179, 31613170.Google Scholar
Singh, O. P., Gidwani, K., Kumar, R., Nylen, S., Jones, S. L., Boelaert, M., Sacks, D. and Sundar, S. (2012). Reassessment of immune correlates in human visceral leishmaniasis as defined by cytokine release in whole blood. Clinical and Vaccine Immunology 19, 961966. doi: 10.1128/CVI.00143-12.Google Scholar
Smelt, S. C., Engwerda, C. R., McCrossen, M. and Kaye, P. M. (1997). Destruction of follicular dendritic cells during chronic visceral leishmaniasis. Journal of Immunology 158, 38133821.Google Scholar
Smelt, S. C., Cotterell, S. E., Engwerda, C. R. and Kaye, P. M. (2000). B cell-deficient mice are highly resistant to Leishmania donovani infection, but develop neutrophil-mediated tissue pathology. Journal of Immunology 164, 36813688.Google Scholar
Soong, L. (2008). Modulation of dendritic cell function by Leishmania parasites. Journal of Immunology 180, 43554360.Google Scholar
Squires, K. E., Schreiber, R. D., McElrath, M. J., Rubin, B. Y., Anderson, S. L. and Murray, H. W. (1989). Experimental visceral leishmaniasis: role of endogenous IFN-gamma in host defense and tissue granulomatous response. Journal of Immunology 143, 42444249.Google Scholar
Stager, S., Smith, D. F. and Kaye, P. M. (2000). Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis. Journal of Immunology 165, 70647071.Google Scholar
Stager, S., Alexander, J., Carter, K. C., Brombacher, F. and Kaye, P. M. (2003). Both interleukin-4 (IL-4) and IL-4 receptor alpha signaling contribute to the development of hepatic granulomas with optimal antileishmanial activity. Infection and Immunity 71, 48044807.Google Scholar
Stager, S., Maroof, A., Zubairi, S., Sanos, S. L., Kopf, M. and Kaye, P. M. (2006). Distinct roles for IL-6 and IL-12p40 in mediating protection against Leishmania donovani and the expansion of IL-10+ CD4+ T cells. European Journal of Immunology 36, 17641771. doi: 10.1002/eji.200635937.Google Scholar
Stanley, A. C. and Engwerda, C. R. (2007). Balancing immunity and pathology in visceral leishmaniasis. Immunology and Cell Biology 85, 138147. doi: 10.1038/sj.icb7100011.Google Scholar
Stanley, A. C., Dalton, J. E., Rossotti, S. H., MacDonald, K. P., Zhou, Y., Rivera, F., Schroder, W. A., Maroof, A., Hill, G. R., Kaye, P. M. and Engwerda, C. R. (2008 a). VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental visceral leishmaniasis. PLOS Pathogens 4, e1000158. doi: 10.1371/journal.ppat.1000158.Google Scholar
Stanley, A. C., Zhou, Y., Amante, F. H., Randall, L. M., Haque, A., Pellicci, D. G., Hill, G. R., Smyth, M. J., Godfrey, D. I. and Engwerda, C. R. (2008 b). Activation of invariant NKT cells exacerbates experimental visceral leishmaniasis. PLOS Pathogens 4, e1000028. doi: 10.1371/journal.ppat.1000028.Google Scholar
Steinman, R. M. and Hemmi, H. (2006). Dendritic cells: translating innate to adaptive immunity. Current Topics in Microbiology and Immunology 311, 1758.Google Scholar
Stern, J. J., Oca, M. J., Rubin, B. Y., Anderson, S. L. and Murray, H. W. (1988). Role of L3T4+ and LyT-2+ cells in experimental visceral leishmaniasis. Journal of Immunology 140, 39713977.Google Scholar
Stober, C. B., Lange, U. G., Roberts, M. T., Alcami, A. and Blackwell, J. M. (2005). IL-10 from regulatory T cells determines vaccine efficacy in murine Leishmania major infection. Journal of Immunology 175, 25172524.Google Scholar
Stober, C. B., Brode, S., White, J. K., Popoff, J. F. and Blackwell, J. M. (2007). Slc11a1, formerly Nramp1, is expressed in dendritic cells and influences major histocompatibility complex class II expression and antigen-presenting cell function. Infection and Immunity 75, 50595067. doi: 10.1128/IAI.00153-07.Google Scholar
Sundar, S., Reed, S. G., Sharma, S., Mehrotra, A. and Murray, H. W. (1997). Circulating T helper 1 (Th1) cell- and Th2 cell-associated cytokines in Indian patients with visceral leishmaniasis. American Journal of Tropical Medicine and Hygiene 56, 522525.Google Scholar
Sunderkotter, C., Kunz, M., Steinbrink, K., Meinardus-Hager, G., Goebeler, M., Bildau, H. and Sorg, C. (1993). Resistance of mice to experimental leishmaniasis is associated with more rapid appearance of mature macrophages in vitro and in vivo. Journal of Immunology 151, 48914901.Google Scholar
Svensson, M., Zubairi, S., Maroof, A., Kazi, F., Taniguchi, M. and Kaye, P. M. (2005). Invariant NKT cells are essential for the regulation of hepatic CXCL10 gene expression during Leishmania donovani infection. Infection and Immunity 73, 75417547. doi: 10.1128/IAI.73.11.7541-7547.2005.Google Scholar
Swihart, K., Fruth, U., Messmer, N., Hug, K., Behin, R., Huang, S., Del Giudice, G., Aguet, M. and Louis, J. A. (1995). Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response. Journal of Experimental Medicine 181, 961971.Google Scholar
Tan, Z. Y., Bealgey, K. W., Fang, Y., Gong, Y. M. and Bao, S. (2009). Interleukin-23: immunological roles and clinical implications. International Journal of Biochemistry and Cell Biology 41, 733735. doi: 10.1016/j.biocel.2008.04.027.CrossRefGoogle ScholarPubMed
Taylor, A. P. and Murray, H. W. (1997). Intracellular antimicrobial activity in the absence of interferon-gamma: effect of interleukin-12 in experimental visceral leishmaniasis in interferon-gamma gene-disrupted mice. Journal of Experimental Medicine 185, 12311239.Google Scholar
Titus, R. G., Sherry, B. and Cerami, A. (1989). Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis. Journal of Experimental Medicine 170, 20972104.Google Scholar
Tolouei, S., Ghaedi, K., Khamesipour, A., Akbari, M., Baghaei, M., Hasheminia, S., Narimani, M. and Hejazi, S. (2012). IL-23 and IL-27 levels in macrophages collected from peripheral blood of patients with healing vs non-healing form of cutaneous leishmaniasis. Iran Journal of Parasitology 7, 1825.Google Scholar
Trinchieri, G. (1998). Interleukin-12: a cytokine at the interface of inflammation and immunity. Advances in Immunology 70, 83243.Google Scholar
Tsagozis, P., Karagouni, E. and Dotsika, E. (2003). CD8(+) T cells with parasite-specific cytotoxic activity and a Tc1 profile of cytokine and chemokine secretion develop in experimental visceral leishmaniasis. Parasite Immunology 25, 569579. doi: 10.1111/j.0141-9838.2004.00672.xPIM672.Google Scholar
Tumang, M. C., Keogh, C., Moldawer, L. L., Helfgott, D. C., Teitelbaum, R., Hariprashad, J. and Murray, H. W. (1994). Role and effect of TNF-alpha in experimental visceral leishmaniasis. Journal of Immunology 153, 768775.Google Scholar
Uzonna, J. E., Joyce, K. L. and Scott, P. (2004 a). Low dose Leishmania major promotes a transient T helper cell type 2 response that is down-regulated by interferon gamma-producing CD8+ T cells. Journal of Experimental Medicine 199, 15591566.Google Scholar
Uzonna, J. E., Spath, G. F., Beverley, S. M. and Scott, P. (2004 b). Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response. Journal of Immunology 172, 37933797.Google Scholar
Vidal, S., Tremblay, M. L., Govoni, G., Gauthier, S., Sebastiani, G., Malo, D., Skamene, E., Olivier, M., Jothy, S. and Gros, P. (1995). The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. Journal of Experimental Medicine 182, 655666.Google Scholar
Von Stebut, E. (2007). Immunology of cutaneous leishmaniasis: the role of mast cells, phagocytes and dendritic cells for protective immunity. European Journal of Dermatology 17, 115122.Google Scholar
von Stebut, E. and Udey, M. C. (2004). Requirements for Th1-dependent immunity against infection with Leishmania major. Microbes and Infection 6, 11021109.Google Scholar
von Stebut, E., Belkaid, Y., Jakob, T., Sacks, D. L. and Udey, M. C. (1998). Uptake of Leishmania major amastigotes results in activation and interleukin 12 release from murine skin-derived dendritic cells: implications for the initiation of anti-Leishmania immunity. Journal of Experimental Medicine 188, 15471552.Google Scholar
Von Stebut, E., Ehrchen, J. M., Belkaid, Y., Kostka, S. L., Molle, K., Knop, J., Sunderkotter, C. and Udey, M. C. (2003). Interleukin 1alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. Journal of Experimental Medicine 198, 191199. doi: 10.1084/jem.20030159.Google Scholar
Wang, Z. E., Reiner, S. L., Zheng, S., Dalton, D. K. and Locksley, R. M. (1994). CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major. Journal of Experimental Medicine 179, 13671371.Google Scholar
Wei, X. Q., Charles, I. G., Smith, A., Ure, J., Feng, G. J., Huang, F. P., Xu, D., Muller, W., Moncada, S. and Liew, F. Y. (1995). Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375, 408411.Google Scholar
Wilson, M. E., Young, B. M., Davidson, B. L., Mente, K. A. and McGowan, S. E. (1998). The importance of TGF-beta in murine visceral leishmaniasis. Journal of Immunology 161, 61486155.Google Scholar
Wilson, M. E., Recker, T. J., Rodriguez, N. E., Young, B. M., Burnell, K. K., Streit, J. A. and Kline, J. N. (2002). The TGF-beta response to Leishmania chagasi in the absence of IL-12. European Journal of Immunology 32, 35563565. doi: 10.1002/1521-4141(200212)32:12<3556::AID-IMMU3556>3.0.CO;2-Q.Google Scholar
Woelbing, F., Kostka, S. L., Moelle, K., Belkaid, Y., Sunderkoetter, C., Verbeek, S., Waisman, A., Nigg, A. P., Knop, J., Udey, M. C. and von Stebut, E. (2006). Uptake of Leishmania major by dendritic cells is mediated by Fcgamma receptors and facilitates acquisition of protective immunity. Journal of Experimental Medicine 203, 177188.CrossRefGoogle ScholarPubMed
Xin, L., Li, K. and Soong, L. (2008). Down-regulation of dendritic cell signaling pathways by Leishmania amazonensis amastigotes. Molecular Immunology 45, 33713382. doi: 10.1016/j.molimm.2008.04.018.Google Scholar
Yoshida, H., Hamano, S., Senaldi, G., Covey, T., Faggioni, R., Mu, S., Xia, M., Wakeham, A. C., Nishina, H., Potter, J., Saris, C. J. and Mak, T. W. (2001). WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection. Immunity 15, 569578.Google Scholar
Zijlstra, E. E. and el-Hassan, A. M. (2001). Leishmaniasis in Sudan. Visceral leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 95 (Suppl. 1), S27S58.Google Scholar