UC Merced

Parasitic infections are a global health burden. The prevention of parasitic disease has relied heavily on mass drug administration campaigns, vector control, and sanitation rather than prevention through vaccination (Mutapi et al. 2013). Among parasites that evade effective vaccine induced immunity is Toxoplasma gondii, a ubiquitous intracellular protozoan that infects approximately one third of the human population and nearly all warm-blooded vertebrates. The adaptive immune response is fundamental to the clearance of T. gondii. Previous work by our lab and others’ with commonly studied T. gondii strains strongly implicates CD8 T cell functions as the primary immune clearance mechanism (Suzuki and Remington, 1988); however, our data also suggests important roles for CD4 T cells and B cells. Using a larger array of T. gondii strains sampled from around the world, we studied the immunological memory response generated in resistant and susceptible mouse genetic backgrounds to secondary infection. We found 1) three host genetic loci determine protective immunological memory responses to T. gondii, 2) dysfunctional marker profiles are highly expressed on both CD8 and CD4 T cells from the susceptible mouse strain, and 3) accumulation of B-1b cells in the resistant mouse strain. We present evidence that two of the genetic loci may determine the observed immune cell phenotypes. Importantly, as antibody producing cells, B cells may present an advantage in the development of effective parasite vaccines as current vaccines are conventionally used to induce antibody responses. Understanding the comprehensive immune response to T. gondii will provide us with both humoral and cell-mediated immune targets to prevent and treat parasitic disease.