Peter E. Kima
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.
- Teaching Interests
- ZOO 4232 - Human Parasitology
- MCB 6772 - Advanced Topics in Cell Biology