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Research in my laboratory focuses on the basis of host immunity to microbial pathogens. In particular, we are examining cellular and molecular responses to the opportunistic protozoan parasite, Toxoplasma gondii, using the mouse as an experimental model. Infection with T.gondii elicits a strong Type 1 cytokine response, characterized by generation of parasite-specific CD4+ and CD8+ T lymphocytes which secrete high levels of the host-protective cytokine, IFN-g.The research in my laboratory is directed towards dissecting early events involved in immunity to this parasite. There are currently two main projects in my lab: 1. Role of neutrophils during toxoplasmosis. We are studying the role of polymorphonuclear leukocytes (PMN) in establishment of immunity to microbial infection. Neutrophils are notableas one of the first cell types to arrive at a site of infection. Recently,we found that PMN are an important early source of IL-12, and that these cells actually prestore the cytokine even in the absence of ongoing infection. We are currently assessing the effects of PMN depletion on the immune response in mice, examining neutrophil interactions with other cells of the immune system, and determining the spectrum of cytokines released by PMN during infection. Further work is directed at localizing the prestored IL-12 at the subcellular level. 2. Host intracellular signaling pathways during Toxoplasma infection.
Toxoplasma is an intracellular parasite, residing within a specialized
vacuole where it replicates until the host cell ruptures. Recent work
in our laboratory is focused on analyzing how intracellular signaling
cascades within the host cell are influenced by the presence of an ongoing
infection. We are particularly interested in determining which signaling
pathways are activated, and which may be disabled, by intracellular infection.
Dr. Denkers is a member of the following Graduate Fields:
Alison Bierly, Graduate Student
Del Rio, L., Butcher, B.A., Bennouna, S., Heiny, S., Sher, A., and E.Y. Denkers. 2004. Toxoplasma gondii triggers MyD88-dependent IL-12 and CCL2 (MCP-1) responses using distinct parasite molecules and host receptors. J. Immunol. 172: 6954-6960. Denkers, E.Y., Butcher, B.A., Del Rio, L., and L. Kim. 2004. Manipulation of MAPK/NFkappaB signaling pathways during intracellular Toxoplasma gondii infection. Immunol. Rev. 201: 191-205. Bennouna, S. and E. Y. Denkers. 2005. Microbial antigen triggers rapid mobilization of TNF-alpha to the neutrophil surface transforming them into inducers of high-level dendritic cell TNF-alpha production. J. Immunol. 174: 4845-4851. Butcher, B.A., Kim, L., Murray, P.J., and E.Y. Denkers. 2005. Cutting Edge: IL-10-independent STAT3 activation by Toxoplasma gondii mediates suppression of IL-12 and TNF-alpha in host macrophages. J. Immunol. 174: 3148-3152. Kim, L., Del Rio, L., Butcher, B.A., Mogensen, T.H., Paludan, S.R., Flavell, R.A., and E.Y. Denkers. 2005. p38 MAPK autophosphorylation drives macrophage IL-12 production during intracellular infection. J. Immunol. 174: 4178-4184. Kim, L., Butcher, B.A., and E.Y. Denkers. 2005. Playing with fire: manipulation
of macrophage proinflammatory signal transduction by the intracellular
protozoan Toxoplasma gondii. Curr. Immunol. Rev. 1: 213-222.
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