CHARACTERIZING THE CNS IMMUNE RESPONSE PROVOKED BY TWO GENETICALLY DIVERGENT STRAINS OF TOXOPLASMA GONDII
PublisherThe University of Arizona.
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AbstractToxoplasma gondii is an obligate intracellular parasite that infects a wide range of intermediate hosts, including humans and rodents. For both humans and rodents, once infected Toxoplasma establishes a lifelong infection in the central nervous system (CNS). In humans, this tropism for the brain underlies Toxoplasma’s ability to cause a wide range of neurological consequences in the immunocompromised, in the developing fetus and occasionally in immunocompetent individuals. The outcomes of symptomatic Toxoplasma infection can range from vision-affecting chorioretinitis to encephalitis to death. Recent human data suggest that the genotype of the infecting Toxoplasma strain may influence disease severity; however, how these strains differ in their ability to cause disease is not well understood. Previous in vitro and acute infection studies in mice have shown that strain-specific polymorphic effector proteins that are secreted and injected into host cells can differentially modulate signaling pathways, affecting cellular functions such as cytokine production. It is unknown if these differences or others lead to strainspecific CNS immune responses. To address this gap in knowledge, we used the mouse model of toxoplasmosis to characterize the neuroinflammatory response generated by two genetically divergent Toxoplasma strains (type II and type III). Using immunohistochemistry and an unbiased stereotyped computer program, Simple PCI, we quantified T cell and macrophage responses in the CNS. We also performed a 25-plex cytokine assay to characterize the CNS cytokine milieu in mice infected with either type II or type III parasites. Remarkably, despite having similar parasite burdens at 3 weeks post infection, we found that type III infection causes a significantly higher number of infiltrating T cells and macrophages/microglia and elicits a more robust pro-inflammatory cytokine milieu compared to type II infection. On-going work is focused on creating transgenic Toxoplasma strains that will enable us to dissect out the role of known effector proteins in these strain-specific neuroinflammatory responses.
Degree ProgramHonors College
Neuroscience and Cognitive Science