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Modulation of innate immunity by African Trypanosomes

Published online by Cambridge University Press:  18 November 2010

DONNA M. PAULNOCK ,
BAILEY E. FREEMAN  and
JOHN M. MANSFIELD
DONNA M. PAULNOCK
Affiliation:
Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA
BAILEY E. FREEMAN
Affiliation:
Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA
JOHN M. MANSFIELD*
Affiliation:
Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA Department of Medical Microbiology & Immunology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA
*
*Contact Information: Professor John M. Mansfield, Department of Bacteriology, 1550 Linden Drive, Microbial Sciences Building, University of Wisconsin-Madison, Madison, WI 53706USA. (E-mail: [email protected])
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Summary

The experimental studies of Brucei group trypanosomes presented here demonstrate that the balance of host and parasite factors, especially IFN-γ GPI-sVSG respectively, and the timing of cellular exposure to them, dictate the predominant MP and DC activation profiles present at any given time during infection and within specific tissues. The timing of changes in innate immune cell functions following infection consistently support the conclusion that the key events controlling host resistance occur within a short time following initial exposure to the parasite GPI substituents. Once the changes in MP and DC activities are initiated, there appears little that the host can do to reverse these changes and alter the final outcome of these regulatory events. Instead, despite the availability of multiple innate and adaptive immune mechanisms that can control parasites, there is an inability to control trypanosome numbers sufficiently to prevent the emergence and establishment of virulent trypanosomes that eventually kill the host. Overall it appears that trypanosomes have carefully orchestrated the host innate and adaptive immune response so that parasite survival and transmission, and alterations of host immunity, are to its ultimate benefit.

Keywords

African trypanosomesinnate immunityimmunoregulationGPI
Type
Research Article
Information
Parasitology , Volume 137 , Special Issue 14: African trypanosomiasis: New insights for disease control , December 2010 , pp. 2051 - 2063
Copyright
Copyright © Cambridge University Press 2010

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References

REFERENCES

Amit, I., Garber, M., Chevrier, N., Leite, A., Donner, Y., Eisenhaure, T., Guttman, M., Grenier, J., Li, W., Zuk, O., Schubert, L., Birditt, B., Shay, T., Goren, A., Zhang, X., Smith, Z., Deering, R., McDonald, R., Cabili, M., Bernstein, B., Rinn, J., Meissner, A., Root, D., Hacohen, N. and Regev, A. (2009). Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses. Science 326, 257–263.CrossRefGoogle ScholarPubMed
Arnold, D. L., Jackson, N. R., Waterfield, W. R. and Mansfield, J. W. (2007). Evolution of microbial virulence: The benefits of stress. Trends in Genetics 23, 293–300.CrossRefGoogle ScholarPubMed
Barkhuizen, M., Magez, S., Atkinson, R. A. and Brombacher, F. (2007). Interleukin-12p70-dependent interferon-gamma production is crucial for resistance in African trypanosomiasis. Journal of Infectious Diseases 196, 1253–1260.CrossRefGoogle ScholarPubMed
Barkhuizen, M., Magez, S., Ryffel, B. and Brombacher, F. (2008). Interleukin-12p70 deficiency increases survival and diminishes pathology in Trypanosoma congolense infection. Journal of Infectious Diseases 198, 1284–1291.CrossRefGoogle ScholarPubMed
Barry, J. D., Le Ray, D. and Herbert, W. J. (1979). Infectivity and virulence of Trypanosoma (Trypanozoon) brucei for mice. IV. Dissociation of virulence and variable antigen type in relation to pleomorphism. Journal of Comparative Pathology 89, 465–470.CrossRefGoogle ScholarPubMed
Bitter, W., Gerrits, H., Kieft, R. and Borst, P. (1998). The role of transferrin-receptor variation in the host range of Trypanosoma brucei. Nature 391, 499–502.CrossRefGoogle ScholarPubMed
Blum, M. L., Down, J. A., Gurnett, A. M., Carrington, M., Turner, M. J. and Wiley, D. C. (1993). A structural motif in the variant surface glycoproteins of Trypanosoma brucei. Nature 362, 603–609.CrossRefGoogle ScholarPubMed
Borst, P., Bitter, W., Blundell, P. A., Chaves, I., Cross, M., Gerrits, H., van Leeuwen, F., McCulloch, R., Taylor, M. and Rudenko, G. (1998). Control of VSG gene expression sites in Trypanosoma brucei. Molecular and Biochemical Parasitology 91, 67–76.CrossRefGoogle ScholarPubMed
Borst, P. and Rudenko, G. (1994). Antigenic variation in African trypanosomes. Science 264(June 24), 1872–1873.CrossRefGoogle ScholarPubMed
Bowdish, D. M. and Gordon, S. (2009 a). Conserved domains of the class a scavenger receptors: Evolution and function. Immunology Reviews 227, 19–31.CrossRefGoogle Scholar
Bowdish, D. M., Sakamoto, K., Kim, M. J., Kroos, M., Mukhopadhyay, S., Leifer, C. A., Tryggvason, K., Gordon, S. and Russell, D. G. (2009 b). Marco, tlr2, and cd14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and mycobacterium tuberculosis. PLoS Pathogens 5, e1000474.CrossRefGoogle ScholarPubMed
Carrington, M., Carnall, N., Crow, M. S., Gaud, A., Redpath, M. B., Wasunna, C. L. and Webb, H. (1998). The properties and function of the glycosylphosphatidylinositol-phospholipase c in Trypanosoma brucei. Molecular and Biochemical Parasitology 91, 153–164.CrossRefGoogle ScholarPubMed
Carrington, M., Walters, D. and Webb, H. (1991). The biology of the glycosylphosphatidylinositol-specific phospholipase c of Trypanosoma brucei. Cell Biology International Reports 15, 1101–1114.CrossRefGoogle ScholarPubMed
Chattopadhyay, A., Jones, N. G., Nietlispach, D., Nielsen, P. R., Voorheis, H. P., Mott, H. R. and Carrington, M. (2005). Structure of the c-terminal domain from Trypanosoma brucei variant surface glycoprotein mitat1.2. Journal of Biological Chemistry 280, 7228–7235.CrossRefGoogle ScholarPubMed
Clayton, C. E. (1978). Trypanosoma brucei: Influence of host strain and parasite antigenic type on infections in mice. Experimental Parasitology 44, 202–208.CrossRefGoogle ScholarPubMed
Coller, S. P., Mansfield, J. M. and Paulnock, D. M. (2003). Glycosylinositolphosphate soluble variant surface glycoprotein inhibits IFN-gamma-induced nitric oxide production via reduction in stat1 phosphorylation in African trypanosomiasis. Journal of Immunology 171, 1466–1472.CrossRefGoogle ScholarPubMed
Coller, S. P. and Paulnock, D. M. (2001). Signaling pathways initiated in macrophages after engagement of type a scavenger receptors. Journal of Leukocyte Biology 70, 142–148.CrossRefGoogle ScholarPubMed
Cross, G. (1990). Cellular and genetic aspects of antigenic variation in trypanosomes. Annual Review of Immunology 8, 83–110.CrossRefGoogle ScholarPubMed
Cross, G. A. (1975). Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Parasitology 71, 393–417.CrossRefGoogle ScholarPubMed
Dagenais, T. R., Demick, K. P., Bangs, J. D., Forest, K. T., Paulnock, D. M. and Mansfield, J. M. (2009 a). T-cell responses to the trypanosome variant surface glycoprotein are not limited to hypervariable subregions. Infection and Immunity 77, 141–151.CrossRefGoogle Scholar
Dagenais, T. R., Freeman, B. E., Demick, K. P., Paulnock, D. M. and Mansfield, J. M. (2009 b). Processing and presentation of variant surface glycoprotein molecules to t cells in African trypanosomiasis. Journal of Immunology 183, 3344–3355.CrossRefGoogle Scholar
De Gee, A. L., Levine, R. F. and Mansfield, J. M. (1988). Genetics of resistance to the African trypanosomes. Vi. Heredity of resistance and variable surface glycoprotein-specific immune responses. Journal of Immunology 140, 283–288.CrossRefGoogle Scholar
De Gee, A. L. and Mansfield, J. M. (1984). Genetics of resistance to the African trypanosomes. Iv. Resistance of radiation chimeras to Trypanosoma rhodesiense infection. Cellular Immunology 87, 85–91.CrossRefGoogle Scholar
De Gee, A. L., Sonnenfeld, G. and Mansfield, J. M. (1985). Genetics of resistance to the African trypanosomes. V. Qualitative and quantitative differences in interferon production among susceptible and resistant mouse strains. Journal of Immunology 134, 2723–2726.CrossRefGoogle Scholar
De Greef, C. and Hamers, R. (1994). The serum resistance-associated (sra) gene of Trypanosoma brucei rhodesiense encodes a variant surface glycoprotein-like protein. Molecular and Biochemical Parasitology 68, 277–284.CrossRefGoogle ScholarPubMed
DeWitte-Orr, S. J., Collins, S. E., Bauer, C. M., Bowdish, D. M. and Mossman, K. L. (2010). An accessory to the ‘trinity’: Sr-as are essential pathogen sensors of extracellular dsRNA, mediating entry and leading to subsequent type i ifn responses. PLoS Pathogens 6, e1000829.CrossRefGoogle Scholar
Donelson, J. E. (1987). Antigenic variation in African trypanosomes. Contributions in Microbiology and Immunology 8, 138–175.Google ScholarPubMed
Drennan, M. B., Stijlemans, B., Van den Abbeele, J., Quesniaux, V. J., Barkhuizen, M., Brombacher, F., De Baetselier, P., Ryffel, B. and Magez, S. (2005). The induction of a type 1 immune response following a Trypanosoma brucei infection is myd88 dependent. Journal of Immunology 175, 2501–2509.CrossRefGoogle ScholarPubMed
Duszenko, M., Ferguson, M. A., Lamont, G. S., Rifkin, M. R. and Cross, G. A. (1985). Cysteine eliminates the feeder cell requirement for cultivation of Trypanosoma brucei bloodstream forms in vitro. Journal of Experimental Medicine 162, 1256–1263.CrossRefGoogle ScholarPubMed
Field, M. C., Menon, A. K. and Cross, G. A. (1991). Developmental variation of glycosylphosphatidylinositol membrane anchors in Trypanosoma brucei. Identification of a candidate biosynthetic precursor of the glycosylphosphatidylinositol anchor of the major procyclic stage surface glycoprotein. Journal of Biological Chemistry 266, 8392–8400.CrossRefGoogle ScholarPubMed
Freymann, D., Down, J., Carrington, M., Roditi, I., Turner, M. and Wiley, D. (1990). 2·9 å resolution structure of the n-terminal domain of a variant surface glycoprotein from Trypanosoma brucei. Journal of Molecular Biology 216, 141–160.CrossRefGoogle ScholarPubMed
Gangloff, M. and Gay, N. J. (2008). Baseless assumptions: Activation of tlr9 by DNA. Immunity 28, 293–294.CrossRefGoogle ScholarPubMed
Gerrits, H., Mussmann, R., Bitter, W., Kieft, R. and Borst, P. (2002). The physiological significance of transferrin receptor variations in Trypanosoma brucei. Molecular and Biochemical Parasitology 119, 237–247.CrossRefGoogle ScholarPubMed
Hager, K. M. and Hajduk, S. L. (1997). Mechanism of resistance of African trypanosomes to cytotoxic human hdl. Nature 385, 823–826.CrossRefGoogle ScholarPubMed
Hajduk, S. L., Hager, K. and Esko, J. D. (1992). High-density lipoprotein-mediated lysis of trypanosomes. Parasitology Today 8, 95–98.CrossRefGoogle ScholarPubMed
Hajduk, S. L., Moore, D. R., Vasudevacharya, J., Siqueira, H., Torri, A. F., Tytler, E. M. and Esko, J. D. (1989). Lysis of Trypanosoma brucei by a toxic subspecies of human high density lipoprotein. Journal of Biological Chemistry 264, 5210–5217.CrossRefGoogle ScholarPubMed
Hajduk, S. L., Smith, A. B. and Hager, K. M. (1995). Hdl-independent lysis of Trypanosoma brucei brucei by human serum. Parasitology Today 11, 444–445.CrossRefGoogle Scholar
Hanrahan, O., Webb, H., O'Byrne, R., Brabazon, E., Treumann, A., Sunter, J. D., Carrington, M. and Voorheis, H. P. (2009). The glycosylphosphatidylinositol-PLC in Trypanosoma brucei forms a linear array on the exterior of the flagellar membrane before and after activation. PLoS Pathogens 5, e1000468.CrossRefGoogle ScholarPubMed
Harris, T. H., Cooney, N. M., Mansfield, J. M. and Paulnock, D. M. (2006). Signal transduction, gene transcription, and cytokine production triggered in macrophages by exposure to trypanosome DNA. Infection and Immunity 74, 4530–4537.CrossRefGoogle ScholarPubMed
Harris, T. H., Mansfield, J. M. and Paulnock, D. M. (2007). Cpg oligodeoxynucleotide treatment enhances innate resistance and acquired immunity to African trypanosomes. Infection and Immunity 75, 2366–2373.CrossRefGoogle ScholarPubMed
Hertz, C. J., Filutowicz, H. and Mansfield, J. M. (1998). Resistance to the African trypanosomes is IFN-gamma dependent. Journal of Immunology 161, 6775–6783.CrossRefGoogle Scholar
Hertz, C. J. and Mansfield, J. M. (1999). Ifn-gamma-dependent nitric oxide production is not linked to resistance in experimental African trypanosomiasis. Cellular Immunology 192, 24–32.CrossRefGoogle Scholar
Hoek, M., Zanders, T. and Cross, G. A. (2002). Trypanosoma brucei expression-site-associated-gene-8 protein interacts with a pumilio family protein. Molecular and Biochemical Parasitology 120, 269–283.CrossRefGoogle ScholarPubMed
Inverso, J. A., De Gee, A. L. and Mansfield, J. M. (1988). Genetics of resistance to the African trypanosomes. VII. Trypanosome virulence is not linked to variable surface glycoprotein expression. Journal of Immunology 140, 289–293.CrossRefGoogle Scholar
Inverso, J. A. and Mansfield, J. M. (1983). Genetics of resistance to the African trypanosomes. II. Differences in virulence associated with vssa expression among clones of Trypanosoma rhodesiense. Journal of Immunology 130, 412–417.CrossRefGoogle Scholar
Inverso, J. A., Uphoff, T. S., Johnson, S. C., Paulnock, D. M. and Mansfield, J. M. (2010). Biological variation among African trypanosomes: I. Clonal expression of virulence is not linked to the variant surface glycoprotein or the variant surface glycoprotein gene telomeric expression site. DNA and Cell Biology 29, 215–227.CrossRefGoogle ScholarPubMed
Kaushik, R. S., Uzonna, J. E., Zhang, Y., Gordon, J. R. and Tabel, H. (2000). Innate resistance to experimental African trypanosomiasis: Differences in cytokine (tnf-alpha, IL-6, IL-10 and IL-12) production by bone marrow-derived macrophages from resistant and susceptible mice. Cytokine 12, 1024–1034.CrossRefGoogle ScholarPubMed
Landeira, D., Bart, J. M., Van Tyne, D. and Navarro, M. (2009). Cohesin regulates VSG monoallelic expression in trypanosomes. Journal of Cell Biology 186, 243–254.CrossRefGoogle ScholarPubMed
Leal, S., Acosta-Serrano, A., Morita, Y. S., Englund, P. T., Bohme, U. and Cross, G. A. (2001). Virulence of Trypanosoma brucei strain 427 is not affected by the absence of glycosylphosphatidylinositol phospholipase c. Molecular and Biochemical Parasitology 114, 245–247.CrossRefGoogle Scholar
Leppert, B. J., Mansfield, J. M. and Paulnock, D. M. (2007). The soluble variant surface glycoprotein of African trypanosomes is recognized by a macrophage scavenger receptor and induces I kappa b alpha degradation independently of traf6-mediated tlr signaling. Journal of Immunology 179, 548–556.CrossRefGoogle ScholarPubMed
Levine, R. F. and Mansfield, J. M. (1981). Genetics of resistance to African trypanosomes: Role of the H-2 locus in determining resistance to infection with Trypanosoma rhodesiense. Infection and Immunity 34, 513–518.CrossRefGoogle ScholarPubMed
Levine, R. F. and Mansfield, J. M. (1984). Genetics of resistance to the African trypanosomes. III. Variant-specific antibody responses of h-2-compatible resistant and susceptible mice. Journal of Immunology 133, 1564–1569.CrossRefGoogle Scholar
Lopez, R., Demick, K. P., Mansfield, J. M. and Paulnock, D. M. (2008). Type i ifns play a role in early resistance, but subsequent susceptibility, to the African trypanosomes. Journal of Immunology 181, 4908–4917.CrossRefGoogle Scholar
Lucas, R., Magez, S., De Leys, R., Fransen, L., Scheerlinck, J. P., Rampelberg, M., Sablon, E. and De Baetselier, P. (1994). Mapping the lectin-like activity of tumor necrosis factor. Science 263, 814–817.CrossRefGoogle ScholarPubMed
MacLean, L., Odiit, M. and Sternberg, J. M. (2001). Nitric oxide and cytokine synthesis in human African trypanosomiasis. Journal of Infectious Diseases 184, 1086–1090.CrossRefGoogle ScholarPubMed
Magez, S., Geuskens, M., Beschin, A., del Favero, H., Verschueren, H., Lucas, R., Pays, E. and de Baetselier, P. (1997). Specific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei. Journal of Cell Biology 137, 715–727.CrossRefGoogle ScholarPubMed
Magez, S., Lucas, R., Darji, A., Songa, E. B., Hamers, R. and De Baetselier, P. (1993). Murine tumour necrosis factor plays a protective role during the initial phase of the experimental infection with Trypanosoma brucei brucei. Parasite Immunology 15, 635–641.CrossRefGoogle Scholar
Magez, S., Radwanska, M., Beschin, A., Sekikawa, K. and De Baetselier, P. (1999). Tumor necrosis factor alpha is a key mediator in the regulation of experimental Trypanosoma brucei infections. Infection and Immunity 67, 3128–3132.CrossRefGoogle ScholarPubMed
Magez, S., Radwanska, M., Drennan, M., Fick, L., Baral, T. N., Brombacher, F. and De Baetselier, P. (2006). Interferon-gamma and nitric oxide in combination with antibodies are key protective host immune factors during Trypanosoma congolense tc13 infections. Journal of Infectious Diseases 193, 1575–1583.CrossRefGoogle ScholarPubMed
Magez, S., Stijlemans, B., Baral, T. and De Baetselier, P. (2002). Vsg-GPI anchors of African trypanosomes: Their role in macrophage activation and induction of infection-associated immunopathology. Microbes and Infection 4, 999–1006.CrossRefGoogle ScholarPubMed
Magez, S., Stijlemans, B., Radwanska, M., Pays, E., Ferguson, M. A. and De Baetselier, P. (1998). The glycosyl-inositol-phosphate and dimyristoylglycerol moieties of the glycosylphosphatidylinositol anchor of the trypanosome variant-specific surface glycoprotein are distinct macrophage-activating factors. Journal of Immunology 160, 1949–1956.CrossRefGoogle ScholarPubMed
Mansfield, J. (2006). The trypanosome “virulence rheostat” and loss of host resistance. Parasite Immunology 28, (Crystal Ball Issue) 262–263.Google Scholar
Mansfield, J. M. and Olivier, M. (2010 b). Immune evasion by parasites. In Immunology of Infectious Diseases. (Eds. Kaufmann, S. H. E., Sher, A., Ahmed, R. and Sacks, D.), ASM Press, Washington, DC. 2, 379–392.Google Scholar
Mansfield, J. M. and Paulnock, D. M. (2005). Regulation of innate and acquired immunity in African trypanosomiasis. Parasite Immunology 27, 361–371.CrossRefGoogle ScholarPubMed
McNeillage, G. J. and Herbert, W. J. (1968). Infectivity and virulence of Trypanosoma (Trypanozoon) brucei for mice. II. Comparison of closely related trypanosome antigenic types. Journal of Comparative Pathology 78, 345–349.CrossRefGoogle ScholarPubMed
Medvedev, A. E., Kopydlowski, K. M. and Vogel, S. N. (2000). Inhibition of lipopolysaccharide-induced signal transduction in endotoxin-tolerized mouse macrophages: Dysregulation of cytokine, chemokine, and toll-like receptor 2 and 4 gene expression. Journal of Immunology 164, 5564–5574.CrossRefGoogle ScholarPubMed
Mensa Wilmot, K., Hereld, D. and Englund, P. T. (1990). Genomic organization, chromosomal localization, and developmentally regulated expression of the glycosyl-phosphatidylinositol-specific phospholipase c of Trypanosoma brucei. Molecular Cell Biology 10, 720–726.Google ScholarPubMed
Metcalf, P., Blum, M., Freymann, D., Turner, M. and Wiley, D. C. (1987). Two variant surface glycoproteins of Trypanosoma brucei of different sequence classes have similar 6 a resolution x-ray structures. Nature 325, 84–86.CrossRefGoogle ScholarPubMed
Milner, J. D. and Hajduk, S. L. (1999). Expression and localization of serum resistance associated protein in Trypanosoma brucei rhodesiense. Molecular and Biochemical Parasitology 104, 271–283.CrossRefGoogle ScholarPubMed
Molina Portela, M. P., Raper, J. and Tomlinson, S. (2000). An investigation into the mechanism of trypanosome lysis by human serum factors. Molecular and Biochemical Parasitology 110, 273–282.CrossRefGoogle ScholarPubMed
Mulligan, H. W. (1970). The African Trypanosomiases. Wiley-Interscience, New York, NY, 950 pp.Google Scholar
Mussmann, R., Janssen, H., Calafat, J., Engstler, M., Ansorge, I., Clayton, C. and Borst, P. (2003). The expression level determines the surface distribution of the transferrin receptor in Trypanosoma brucei. Molecular Microbiology 47, 23–35.CrossRefGoogle ScholarPubMed
Namangala, B., Brys, L., Magez, S., De Baetselier, P. and Beschin, A. (2000). Trypanosoma brucei brucei infection impairs mhc class II antigen presentation capacity of macrophages. Parasite Immunology 22, 361–370.CrossRefGoogle ScholarPubMed
Navarro, M. and Gull, K. (2001). A pol i transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei. Nature 414, 759–763.CrossRefGoogle Scholar
Paulnock, D. M. (1992). Macrophage activation by T cells. Current Opinion in Immunology 4, 344–349.CrossRefGoogle ScholarPubMed
Paulnock, D. M. (1994). The molecular biology of macrophage activation. Immunology Series 60, 47–62.Google ScholarPubMed
Paulnock, D. M. (Ed). (2000). Macrophages. The Practical Approach Series. New York, NY, Oxford University Press.CrossRefGoogle Scholar
Paulnock, D. M. and Coller, S. P. (2001). Analysis of macrophage activation in African trypanosomiasis. Journal of Leukocyte Biology 69, 685–690.CrossRefGoogle ScholarPubMed
Paulnock, D. M., Demick, K. P. and Coller, S. P. (2000). Analysis of interferon-gamma-dependent and -independent pathways of macrophage activation. Journal of Leukocyte Biology 67, 677–682.CrossRefGoogle ScholarPubMed
Paulnock, D. M., Smith, C. and Mansfield, J. M. (1989). Antigen Presenting Cell Function in African Trypanosomiasis. Alan, R.Liss Inc, New York, 135–144.Google Scholar
Raper, J., Fung, R., Ghiso, J., Nussenzweig, V. and Tomlinson, S. (1999). Characterization of a novel trypanosome lytic factor from human serum. Infection and Immunity 67, 1910–1916.CrossRefGoogle ScholarPubMed
Raper, J., Portela, M. P., Lugli, E., Frevert, U. and Tomlinson, S. (2001). Trypanosome lytic factors: Novel mediators of human innate immunity. Current Opinion in Microbiology 4, 402–408.CrossRefGoogle ScholarPubMed
Reinitz, D. M., Aizenstein, B. D. and Mansfield, J. M. (1992). Variable and conserved structural elements of trypanosome variant surface glycoproteins. Molecular and Biochemical Parasitology 51, 119–132.CrossRefGoogle ScholarPubMed
Rifkin, M. R. (1978). Trypanosoma brucei: Some properties of the cytotoxic reaction induced by normal human serum. Experimental Parasitology 46, 189–206.CrossRefGoogle ScholarPubMed
Schleifer, K. W., Filutowicz, H., Schopf, L. R. and Mansfield, J. M. (1993 a). Characterization of T helper cell responses to the trypanosome variant surface glycoprotein. Journal of Immunology 150, 2910–2919.CrossRefGoogle Scholar
Schleifer, K. W. and Mansfield, J. M. (1993 b). Suppressor macrophages in African trypanosomiasis inhibit T cell proliferative responses by nitric oxide and prostaglandins. Journal of Immunology 151, 5492–5503.CrossRefGoogle ScholarPubMed
Schopf, L. R., Filutowicz, H., Bi, X. J. and Mansfield, J. M. (1998). Interleukin-4-dependent immunoglobulin g1 isotype switch in the presence of a polarized antigen-specific Th1-cell response to the trypanosome variant surface glycoprotein. Infection and Immunity 66, 451–461.CrossRefGoogle Scholar
Smith, A. B., Esko, J. D. and Hajduk, S. L. (1995). Killing of trypanosomes by the human haptoglobin-related protein. Science 268, 284–286.CrossRefGoogle ScholarPubMed
Sternberg, J. M., Rodgers, J., Bradley, B., MacLean, L., Murray, M. and Kennedy, P. G. (2005). Meningoencephalitic African trypanosomiasis: Brain IL-10 and IL-6 are associated with protection from neuro-inflammatory pathology. Journal of Neuroimmunology 167, 81–89.CrossRefGoogle ScholarPubMed
Steverding, D., Stierhof, Y. D., Chaudhri, M., Ligtenberg, M., Schell, D., Beck Sickinger, A. G. and Overath, P. (1994). Esag 6 and 7 products of Trypanosoma brucei form a transferrin binding protein complex. European Journal of Cell Biology 64, 78–87.Google Scholar
Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., Frazier, W. A., Lacy-Hulbert, A., Khoury, J. E., Golenbock, D. T. and Moore, K. J. (2010). Cd36 ligands promote sterile inflammation through assembly of a toll-like receptor 4 and 6 heterodimer. Nature Immunoligy 11, 155–161.CrossRefGoogle ScholarPubMed
Stijlemans, B., Baral, T. N., Guilliams, M., Brys, L., Korf, J., Drennan, M., Van Den Abbeele, J., De Baetselier, P. and Magez, S. (2007). A glycosylphosphatidylinositol-based treatment alleviates trypanosomiasis-associated immunopathology. Journal of Immunology 179, 4003–4014.CrossRefGoogle ScholarPubMed
Tachado, S. D., Gerold, P., Schwarz, R., Novakovic, S., McConville, M. and Schofield, L. (1997). Signal transduction in macrophages by glycosylphosphatidylinositols of plasmodium, Trypanosoma, and Leishmania: Activation of protein tyrosine kinases and protein kinase c by inositolglycan and diacylglycerol moieties. Proceedings of the National Academy of Sciences, USA 94, 4022–4027.CrossRefGoogle ScholarPubMed
Todt, J. C., Hu, B. and Curtis, J. L. (2008). The scavenger receptor sr-a i/ii (cd204) signals via the receptor tyrosine kinase mertk during apoptotic cell uptake by murine macrophages. Journal of Leukocyte Biology 84, 510–518.CrossRefGoogle ScholarPubMed
Uzonna, J. E., Kaushik, R. S., Gordon, J. R. and Tabel, H. (1999). Cytokines and antibody responses during Trypanosoma congolense infections in two inbred mouse strains that differ in resistance. Parasite Immunology 21, 57–71.CrossRefGoogle ScholarPubMed
Van-der-Ploeg, L. H., Gottesdiener, K. and Lee, M. G. (1992). Antigenic variation in African trypanosomes. Trends in Genetics 8, 452–457.CrossRefGoogle ScholarPubMed
Vickerman, K. and Luckins, A. G. (1969). Localization of variable antigens in the surface coat of Trypanosoma brucei using ferritin conjugated antibody. Nature 224, 1125–1126.CrossRefGoogle ScholarPubMed
Wang, J., Bohme, U. and Cross, G. A. (2003). Structural features affecting variant surface glycoprotein expression in Trypanosoma brucei. Molecular and Biochemical Parasitology 128, 135–145.CrossRefGoogle ScholarPubMed
Webb, H., Carnall, N. and Carrington, M. (1994). The role of GPI-PLC in Trypanosoma brucei. Brazilian Journal of Medical and Biological Research 27, 349–356.Google ScholarPubMed
Webb, H., Carnall, N., Vanhamme, L., Rolin, S., Van Den Abbeele, J., Welburn, S., Pays, E. and Carrington, M. (1997). The GPI-phospholipase c of Trypanosoma brucei is non-essential but influences parasitemia in mice. Journal of Cell Biology 139, 103–114.CrossRefGoogle Scholar
Xong, H. V., Vanhamme, L., Chamekh, M., Chimfwembe, C. E., Van Den Abbeele, J., Pays, A., Van Meirvenne, N., Hamers, R., De Baetselier, P. and Pays, E. (1998). A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell 95, 839–846.CrossRefGoogle ScholarPubMed
Yew, K. H., Carsten, B. and Harrison, C. (2010). Scavenger receptor a1 is required for sensing hcmv by endosomal tlr-3/-9 in monocytic Thp-1 cells. Molecular Immunology 47, 883–893.CrossRefGoogle ScholarPubMed