Peter E. Kima

Associate Professor

Department of Microbiology and Cell Science University of Florida 
Ph.D. (1992) Molecular Biology and Biotechnology Hahnemann University, Philadelphia PA

Postdoctoral: 1992-1999, Yale University - Department of Epidemiology and Public Health,
Department of Microbial Pathogenesis, School of Medicine.

Teaching Interest

Parasitology

Description of Research

General areas: My laboratory is interested in the mechanisms by which intracellular pathogens evade immune detection. The capacity to evade immune detection is crucial for pathogenesis.

Our preferred intracellular pathogens are protozoan parasites of the Leishmania spp. These organisms preferentially infect macrophages wherein they reside and replicate in a fusion competent vacuole (parasitophorous vacuole). Unlike other intracellular pathogens that have evolved intriguing strategies to avoid interaction with host lysosomes, Leishmania parasites enter the endocytic pathway and thrive in a lysosomal environment. Nonetheless recent evidence has shown that these parasites can modulate access of their antigens into the MHC class II pathway of antigen presentation, a process referred to as antigen sequestration. We want to know how they do it.

The studies in this area are guided by the hypothesis that the characteristics of the parasitophorous vacuole, which lead to antigen sequestration, are determined in part by the molecule(s) employed by the parasite to gain entry into the cell. To demonstrate that parasitophorous vacuolar characteristics are dependent on the internalization receptor employed, we are studying infection of macrophage cell lines lacking surface molecules that have been implicated in parasite entry. These molecules include complement receptors, mannose receptor, scavenger receptor and the Fc receptors. This analysis will also include macrophages lacking molecules which mediate signaling from these receptors. Some signaling molecules of interest include the tyrosine kinase syk and members of the Src-family of tyrosine kinases. These cell lines are being derived from knockout animals.

With these reagents we should be in position to follow the evolution of phagosome characteristics by tracking the interaction of this compartment with known markers along the endocytic pathway, in microscopic studies or by subcellular fractionation. Changes in processing of parasite derived antigens upon infection of these mutant cells will be obtained from antigen presentation experiments employing antigen specific T-T hybridomas.

The other interest of the lab is assessing how the choice to infect different hematopoeitic cells impacts on Leishmania pathogenesis. Specifically, in the short term we would like to determine the contribution of dendritic cells to the pathogenesis of Leishmania. We are in the process of acquiring mice with developmental defects in dendritic cells for these studies.

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Selected Publications

Kima P.E., S. L. Constant, L. Harnum, M. Colmanares, K.S. Lee, A.M. Haberman, M.J. Shlomchik and D. McMahon-Pratt. Internalization of Leishmania mexicana complex amastigotes via the Fc receptor is required to sustain infection in murine cutaneous leishmaniasis. Submitted.

McMahon-Pratt D., P.E. Kima and L. Soong. 1998. Leishmania amastigote target antigens: the challenge of a stealthy intracellular parasite. Parasitology Today. 14:31-34.

Kima P.E., N.H. Ruddle, and D. McMahon-Pratt. 1997. Presentation via the class I pathway by L. amazonensis-infected macrophages of an endogenous leishmanial antigen to CD8+ T cells. J. Immunol. 159:1828-1834.

Kima P.E., L. Soong, C. Chicharo, N.H. Ruddle, and D. McMahon-Pratt. 1996. Leishmania promote sequestration of endogenously synthesized parasite antigen from presentation by infected macrophages to CD4+ T cells. Eur. J. Immunol. 26:3163-3169.

Soong, L., J. Xu, I.S. Grewal, P. Kima, J. Sun, B.J. Longley Jr., N.H. Ruddle, D. McMahon-Pratt and R.A. Flavell. 1996. Disruption of CD40/CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection. Immunity. 4:263-273

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