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| Dr. Wilson's research focuses on the molecular and immunobiology of infection with the protozoan parasite, Leishmania | ||||||
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Dr. Wilson's research focuses on the immuno- and molecular biology of infection with the protozoan parasite, Leishmania chagasi, a cause of the disease visceral leishmaniasis. Leishmania are obligate intracellular parasites of macrophages. The outcome of this parasitic infection is the result of a dynamic balance between parasite virulence factors and the local mammalian host environment. Aspects of this interaction under study include the initial inflammatory response to infection,during which the parasite attracts and is intially taken into neutrophils, and ultimately transferred to local tissue macrophages. The outcome of the adaptive immune response is dependent on local cytokines and immune cells that promote either a type 1 curative, or anti-inflammatory (e.g. transforming growth factor-β, IL-10) response. We study parasite factors modifying the local immune response, including the major surface protease MSP, and other proteases and factors secreted by the parasite into the host environment.
Leishmania are phagocytosed through receptors located in cholesterol-enriched microdomains of the macrophage surface, causing aggregates of polymerized actin and migration into a compartment that delays fusion with lysosomes for >24 hrs. Different pathways are utilized by the different Leishmania life forms, uniquely suited to the intracellular needs of that life stage. Using confocal and electron microscopy the lab is investigating the routes through which the parasite moves into the infected cell and how these relate to intracellular survival. In addition, we are characterizing the dramatic switches in expression of macrophage transcripts and microRNAs induced during leishmania phagocytosis. Humans living in endemic areas develop widely divergent outcomes of L. chagasi infection, ranging from spontaneous cure to progressive, fatal visceral leishmaniasis. In collaboration with professors in northeast Brazil, India and Australia, Dr. Wilson’s group is examining the hypothesis that polymorphic alleles at immune response genes contribute to an individual’s susceptibility to develop different outcomes after infection. |
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| Selected Publications | ||||||
| Click Here for a Complete List of Articles | ||||||
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Jeronimo, S.M.B., Holst, A.K.B., Jamieson, S.E., Francis, R., Martins, D.R.A., Ettinger, N., Nascimento, E.T., Miller, E.N., Cordell, H.J., Duggal, P., Beaty, T.H., Blackwell, J.M. and Wilson M.E. Genes at human chromosome 5q31.1 regulate delayed type hypersensitivity responses associated with Leishmania chagasi infection. Genes and Immunity: 8:539-551, 2007.
Jeronimo, S.M.B., Duggal, P., Ettinger, N.A., Nascimento, E.T., Martins, D.R.A., Monteiro, G., Pearson, R.D., Blackwell, J.M., Beaty, T.H., and Wilson M.E. Genetic predisposition to self-curing infection with the protozoan Leishmania chagasi: A genome wide scan. J. Infect. Dis. 196:1261-1269, 2007. Gaur, U., Roberts, S.C., Dalvi, R.P., Corraliza, I., Ullman, B. and Wilson M.E. An effect of parasite-encoded arginase on the outcome of murine cutaneous leishmaniasis. J. Immunology: 179:8446-8453, 2007. Hsiao, C.-H.C., Yao, C., Storlie, P.A., Donelson, J.E. and Wilson M.E. The major surface protease (MSP or GP63) in the intracellular amastigote life stage of Leishmania chagasi. Mol. Biochem. Parasitol.: 157(2): 148-159, 2008. Ettinger, N.A. and Wilson M.E. Macrophage and T-cell gene expression in a model of early infection with the protozoan, Leishmania chagasi. PLoS Negl Trop Dis 2(6): e252 and cover illustration. Ettinger, N.A., Duggal, P., Braz, R.F.S., Nascimento, E.T., Beaty, T.H., Jeronimo, S.M.B., Pearson, R.D., Blackwell, J.M., Moreno, L. and Wilson M.E. Genetic Admixture in Northeast Brazilians Exposed to Infection with the Protozoan Parasite Leishmania chagasi. Annals of Human Genetics: In press. |
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| Department/Program Affiliations |
| Internal Medicine |
| MSTP |
| Biosciences |
| Immunology |
| Microbiology |
| Molecular and Cellular Biology |