Research Interests
Immunology of Chronic Leishmania Infection
IgG and FcgammaR interactions
IL-10 responses
Parasite Immunology
Key words: immunology, immunoparasitology, Leishmania, parasite, IL-10, Fcgamma R, cysteine proteinase
Research Details
Worldwide there are 12 million people infected with the single-celled parasite Leishmania, with 2 million new infections a year. Spread by sandfly bites, this parasite causes fatal disease of the internal organs as well as non-healing and potentially disfiguring diseases of the skin and mucous membranes. Thirteen Gulf War veterans contracted an unusual version of leishmaniasis that affected the internal organs, even though this strain exclusively causes skin disease in local populations. Over 1200 cases of cutaneous leishmaniasis have occurred in the US troops stationed in Iraq and Afghanistan.
We have been studying infection of mice by Leishmania mexicana, attempting to understand why this parasite causes non-healing disease, whereas a related parasite, L. major, causes lesions that heal. We have found that the cytokine IL-10 suppresses a protective T cell-mediated IFN-gamma response and that IL-10 is therefore required for chronic infection. IL-10 production is triggered by antibodies on the surface of parasites. FcgammaR, likely on macrophages, are also required for chronic disease to occur. We are trying to determine the IgG isotypes and FcγR types involved in this IL-10 process as well as the cellular source of IL-10 (macrophages, T cells, B cells, other?) in order to better understand the mechanism of this suppressive response and to help guide vaccine development. More recently we began new investigations into the role of glycolipids as parasite surface targets of IgG.
A better understanding of the immune mechanisms of Leishmania infection may give insights into many other diseases that involve cell-mediated immunity, especially those caused by pathogens that live inside host cells such as tuberculosis, toxoplasmosis, and HIV.
Rotation Projects for 2009-2010
We are studying the immunology of chronic cutaneous leishmaniasis. In particular we are concentrating on the role of FcgammaR on macrophages and their role in inducing IL-10, which suppresses the protective immune response. We have also recently begun to study the role of glycolipids as antigens, possibly presented by CD-1, an MHC-like molecule that presents glycolipid antigens rather than peptides. These glycolipids may be responsible for IgG responses that in turn generate the suppressive IL-10 response. This project involves glycolipid biochemistry as well as immunology. A rotation project could involve testing human serum samples from L. mexicana-infected people to see if the antibody responses seen in mice to glycolipids occur in humans as well. Analysis of the epitopes on the glycolpids that are recognized by antibodies is also a feasible project. Also testing CD1 tetramer binding to parasite glycolipids and NKT cells can be done.
Lab personnel:
Dr. Niansheng Chu- Research Specialist/Lab Manager
Supriya Patel- Research Specialist
Infectious Diseases
General Internal Medicine
Selected Publications
Buxbaum, L.U. : Type I IFNs promote the early IFN-γ response and the IL-10 response in Leishmania mexicana infection. Parasite Immunology 31: 153-160, 2010.
Buxbaum, L.U. : A detrimental role for IgG and FcgammaR in Leishmania mexicana infection. Immunol. Res. 42(1-3): 197-209, 2008.
Thomas, B.N., and Buxbaum, L.U. : FcγRIII mediates immunoglobulin G-induced interleukin-10 and is required for chronic Leishmania mexicana lesions.
Infect. Immun. 76: 623-631, 2008.
Buxbaum, L.U. and Scott, P.: Interleukin 10- and Fcgamma receptor-deficient mice resolve Leishmania mexicana lesions. Infect. Immun. 73: 2101-8, 2005.
Buxbaum, L.U., Denise, H., Coombs, G.H., Alexander, J., Mottram, J.C., and Scott, P.: Cysteine protease B of Leishmania mexicana inhibits host Th1 responses and protective immunity. J. Immunol. 171: 3711-17, 2003.
Buxbaum, L.U., Uzonna, J.E., Goldschmidt, M.H., and Scott, P.: Control of New World cutaneous leishmaniasis is interleukin-12 independent but STAT4 dependent. Euro. J. Immunol. 32: 3206-3215, 2002.
Morita, Y.S., Acosta-Serrano, A., Buxbaum, L.U. and Englund, P.T.: Glycosyl phosphatidylinositol myristoylation in African trypanosomes. New intermediates in the pathway for fatty acid remodeling. J. Biol. Chem. 275: 14147-14154, 2000.
Jones, D.E., Buxbaum, L.U., and Scott, P.: IL-4 independent inhibition of IL-12 responsiveness during Leishmania amazonensis infection. J. Immunol. 165: 364-372, 2000.
Buxbaum, L.U., Milne, K.G., Werbovetz, K.A. and Englund, P.T.: Myristate exchange on the Trypanosoma brucei variant surface glycoprotein. Proc. Natl. Acad. Sci. USA 93: 1178-1183, 1996.
Doering, T.L., Raper, J., Buxbaum, L.U., Adams, S.P., Gordon, J.I., Hart, G.W. and Englund, P.T.: An analog of myristic acid with selective toxicity for African trypanosomes. Science 252: 1851-1854, 1991.
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Last updated: 02/08/2013
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