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The involvement of TLR2 in cytokine and reactive oxygen species (ROS) production by PBMCs in response to Leishmania major phosphoglycans (PGs)

Published online by Cambridge University Press:  27 July 2009

G. KAVOOSI ,
S. K. ARDESTANI  and
A. KARIMINIA
G. KAVOOSI*
Affiliation:
Institute of Biotechnology, University of Shiraz, Shiraz, Iran
S. K. ARDESTANI
Affiliation:
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
A. KARIMINIA
Affiliation:
Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
*
*Corresponding author: Institute of Biotechnology, University of Shiraz, Shiraz, Iran. PO Box 71441-65186. Tel: +98 (711) 2272805. Fax: +98 (711) 2272805. E-mail: [email protected]
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Summary

In the present study, we show for the first time that lipophosphoglycan (LPG) stimulated cytokine production by human peripheral blood mononuclear cells is also mediated via Toll-like receptor (TLR2). In addition, in order to verify if TLR2 is involved in recognition of the purified PGs, neutralizing mAbs against TLR2 and TLR4 were used to treat the cells before being stimulated with PGs. We found strong Th1-promoting cytokines induced by sLPG but not by mLPG which was blocked by presence of anti-TLR2 mAb. This finding reveals a mechanism by which the first encounter and recognition of L. major promastigotes by mLPG after interaction with TLR2 provides a cytokine milieu for consequent Th2 differentiation. Moreover, having shown the strong induction of Th1-promoting cytokines and low production of IL-10 in response to sLPG might have vaccine implication since it is recognized by TLR2 providing signals to professional antigen presenting cells that reside in the skin to promote effective T cell responses against Leishmania infection. In addition, it was shown that purified mLPG and sLPG activate reactive oxygen species (ROS) production which is also blocked by anti-TLR2 but not by anti-TLR4. However, no inhibition was seen in PPG-induced cytokine and ROS production in the presence of anti-TLR2 and anti-TLR4, implying involvement of other receptors.

Keywords

Leishmania majorphosphoglycanperipheral blood mononuclear cellToll-like receptorreactive oxygen speciescytokine
Type
Research Article
Information
Parasitology , Volume 136 , Issue 10 , September 2009 , pp. 1193 - 1199
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

Aderem, A. and Ulevitch, R. J. (2000). Toll-like receptors in the induction of the innate immune response. Nature, London 406, 782–787.CrossRefGoogle ScholarPubMed
Amato, V. S., Tuon, F. F., Bacha, H. A., Neto, V. A. and Nicodemo, A. C. (2008). Mucosal leishmaniasis. Current scenario and prospects for treatment. Acta Tropica 105, 1–9.CrossRefGoogle ScholarPubMed
Becker, I., Salaiza, N., Aguirre, M., Delgado, J., Carrillo-Carrasco, N., Kobeh, L. G., Ruiz, A., Cervantes, R., Torres, A. P., Cabrera, N., Gonzalez, A., Maldonado, C. and Isibasi, A. (2003). Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor2. Molecular and Biochemical Parasitology 130, 65–74.CrossRefGoogle Scholar
Brodsky, I. and Medzhitov, R. (2007). Two modes of ligand recognition by TLRs. Cell 130, 979–981.CrossRefGoogle ScholarPubMed
Buwitt-Beckmann, U., Heine, H., Wiesmuller, K. H., Jung, G., Brock, R. and Ulmer, A. J. (2005). Lipopeptide structure determines TLR2 dependent cell activation level. FEBS Journal 272, 6354–6364.CrossRefGoogle ScholarPubMed
Charmoy, M., Megnekou, R., Allenbach, C., Zweifel, C., Perez, C., Monnat, K., Breton, M., Ronet, C., Launois, P. and Tacchini-Cottier, F. (2007). Leishmania major induces distinct neutrophil phenotypes in mice that are resistant or susceptible to infection. Journal of Leukocyte Biology 82, 288–299.CrossRefGoogle ScholarPubMed
Conour, J. E., Graham, W. V. and Gaskins, H. R. (2004). A combined in vitro/bioinformatic investigation of redox regulatory mechanisms governing cell cycle progression. Physiological Genomics 18, 196–205.CrossRefGoogle ScholarPubMed
De Veer, M. J., Curtis, J. M., Baldwin, T. M., Di Donato, J. A., Sexton, A., McConville, M. J., Handman, E. and Schofield, L. (2003). MyD88 is essential for clearance of Leishmania major: possible role for lipophosphoglycan and Toll-like receptor 2 signaling. European Journal of Immunology 33, 2822–2831.CrossRefGoogle ScholarPubMed
Dermine, J. F., Scianimanico, S., Prive, C., Descoteaux, A. and Desjardins, M. (2000). Leishmania promastigotes require lipophosphoglycan to actively modulate the fusion properties of phagosomes at an early step of phagocytosis. Cellular Microbiology 2, 115–126.CrossRefGoogle ScholarPubMed
Flandin, J. F., Chano, F. and Descoteaux, A. (2006). RNA interference reveals a role for TLR2 and TLR3 in the recognition of Leishmania donovani promastigotes by interferon-gamma-primed macrophages. European Journal of Immunology 36, 411–420.CrossRefGoogle ScholarPubMed
Greenblatt, C. L., Slutzky, G. M., De Ibarra, A. A. L. and Snary, D. (1983). Monoclonal antibodies for serotyping Leishmania strains. Journal of Clinical Microbiology 18, 191–193.CrossRefGoogle ScholarPubMed
Handman, E. (1999). Cell biology of Leishmania. Advances in Parasitology 44, 1–39.CrossRefGoogle ScholarPubMed
Ilg, T. (2000). Proteophosphoglycan of Leishmania. Parasitology Today 16, 489–497.CrossRefGoogle ScholarPubMed
Ilg, T., Stierhof, Y. D., Craik, D., Simpson, R., Handman, E. and Bacic, A. (1996). Purification and structural characterization of a filamentous, mucin-like proteophosphoglycan secreted by Leishmania parasites. Journal Biological Chemistry 271, 21583–21596.CrossRefGoogle ScholarPubMed
Kavoosi, G., Ardestani, S. K., Kariminia, A., Zeinali, M. and Alimohammadian, M. H. (2008). Leishmania major: Effects of proteophosphoglycan on reactive oxygen species, IL-12, IFN-γ and IL-10 production in healthy individuals. Experimental Parasitology 120, 62–66.CrossRefGoogle ScholarPubMed
Kavoosi, G., Ardestani, S. K., Kariminia, A., Abolhassani, M. and Turco, S. J. (2006). Leishmania major: Reactive oxygen species and interferon gamma induction by soluble lipophosphoglycan of stationary phase promastigotes. Experimental Parasitology 114, 323–328.CrossRefGoogle ScholarPubMed
Khan, S., Weterings, J. J., Britten, C. M., de Jong, A. R., Graafland, D., Melief, C. J., van der Burg, S. H., van der Marel, G., Overkleeft, H. S., Filippov, D. V. and Ossendorp, F. (2009). Chirality of TLR-2 ligand Pam(3)CysSK(4) in fully synthetic peptide conjugates critically influences the induction of specific CD8(+) T-cells. Molecular Immunology 46, 1084–1091.CrossRefGoogle Scholar
Locksley, R. M. and Louis, J. A. (1992). Immunology of leishmaniasis. Current Opinion in Immunology 4, 413–418.CrossRefGoogle ScholarPubMed
McConville, M. J., Homans, S. W., Thomas-Oates, J. E., Dell, A. and Bacic, A. (1990). Structure of the glycoinositolphospholipids from Leishmania major. A family of novel galactofuranose containing glycolipids. Journal of Biological Chemistry 265, 7385–7394.CrossRefGoogle ScholarPubMed
McConville, M. J., Schnur, L. F., Jaffe, C. and Schneider, P. (1995). Structure of Leishmania lipophosphoglycan: inter- and intraspecific polymorphism in old world species. The Biochemical Journal 310, 807–818.CrossRefGoogle ScholarPubMed
McConville, M. J., Turco, S. J., Ferguson, M. A. and Sacks, D. L. (1992). Developmental modification of lipophosphoglycan during the differentiation of Leishmania major promastigotes to an infectious stage. EMBO Journal 11, 3593–3600.CrossRefGoogle Scholar
Pasare, C. and Medzhitov, R. (2003). Toll pathway-dependent blockade of CD4+/CD25+ T cell-mediated suppression by dendritic cells. Science 299, 1033–1036.CrossRefGoogle ScholarPubMed
Pinheiro, R. O., Pinto, E. F., Guedes, H. L., Filho, O. A., de Mattos, K. A., Saraiva, E. M., de Mendonça, S. C. and Rossi-Bergmann, B. (2007). Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan. Vaccine 25, 2716–2722.CrossRefGoogle ScholarPubMed
Takeda, K., Kaisho, T. and Akira, S. (2002). Toll-like receptors. Annual Review Immunology 21, 335–376.CrossRefGoogle Scholar
Turco, S. J., Wilkerson, M. A. and Clawsons, D. R. (1984). Expression of an unusual acidic glycoconjugate in Leishmania donovanis. Journal of Biological Chemistry 259, 3883–3889.CrossRefGoogle Scholar
Van Der Kleij, D., Latz, E., Brouwers, J. F., Kruize, Y. C., Schmitz, M., Kurt-Jones, E. A., Espevik, T., de Jong, E. C., Kapsenberg, M. L., Golenbock, D. T., Tielens, A. G. and Yazdanbakhsh, M. (2002). A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. Journal of Biological Chemistry 277, 48122–48129.CrossRefGoogle ScholarPubMed
Villasenor-Cardoso, M. I., Salaiza, N., Delgado, J., Gutierrez-Kobeh, L., Perez-Torres, A. and Becker, I. (2008). Mast cells are activated by Leishmania mexicana LPG and regulate the disease outcome depending on the genetic background of the host. Parasite Immunology 30, 425–434.CrossRefGoogle ScholarPubMed
Wang, B., Henao-Tamayo, M., Harton, M., Ordway, D., Shanley, C., Basaraba, R. J. and Orme, I. M. (2007). A Toll-like receptor-2-directed fusion protein vaccine against tuberculosis. Clinical and Vaccine Immunology 14, 902–906.CrossRefGoogle ScholarPubMed
Zambrano-Villa, S. D., Rosales-Borjas, J. C. and Ortiz-Ortiz, L. (2002). How protozoan parasites evade the immune response. Trends in Parasitology 18, 272–278.CrossRefGoogle ScholarPubMed
Zhang, X., Chentoufi, A. A., Dasgupta, G., Nesburn, A. B., Wu, M., Zhu, X., Carpenter, D., Wechsler, S. L., You, S. and BenMohamed, L. (2009). A genital tract peptide epitope vaccine targeting TLR 2 efficiently induces local and systemic CD8+T cells and protects against herpes simplex virus type 2 challenge. Mucosal Immunology 2, 129–143.CrossRefGoogle ScholarPubMed