THE ROLE OF NEUTROPHILS IN TOXOPLASMOSIS

Cornell University Ithaca, Ithaca NY

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Abstract

Toxoplasma gondii is an obligate, intracellular protozoan parasite, which causes morbidity and mortality in a broad range of species, including human beings. As an opportunistic organs, its importance as a pathogen has resurfaced with the AIDS epidemic. It has been estimated that approximately 30% of AIDS patients suffer from reactivation of infection. In mice, T. gondii induces a strong and protective cell mediated immune response which is driven by early IL-12 production. Several cell types elaborate IL-12 and may participate in this early priming of the immune response. These include activated macrophages and dendritic cells. Recently, neutrophils have been shown to produce IL-12 rapidly in response to several microbial pathogens. We hypothesize that neutrophils not only synthesize and release IL-12 (and other immunoregulatory cytokines and chemokines) in response to T. gondii but also influence the developing immune system in vivo, ultimately impacting survival. To address this hypothesis, we will investigate cytokine and chemokine production by neutrophils and their effect on adaptive immunity. To do this, we will examine cytokine and chemokine production by neutrophils and their effect on adaptive immunity. To do this, we will examine cytokine and chemokine production in isolated neutrophils and follow development of the immune response in granulocyte-depleted mice. Since neutrophils possess numerous effector mechanisms in addition to cytokine production (e.g., killing mechanisms), we will also investigate the production and effects of R0I, RNI, and several granule constituents on survival of T. gondii. Overall, our goal is to determine the role of neutrophils in influencing the immune response during toxoplasmosis.