In Search Of Trojan Horses: Characterizing Early Cell Targets Of Toxoplasma Gondii
Toxoplasma gondii is a master manipulator of the immune response, modulating proinflammatory cytokine production from host cells, blocking apoptotic pathways, and altering motility of infected cells. In these studies, I identify a Gr-1-expressing subset of dendritic cells hijacked by the parasite as a vehicle for dissemination from the inoculation site after intraperitoneal infection. These DC are preferentially infected compared to other cell types in the peritoneal cavity, and they migrate to the spleen in partial dependence on CCR2 signaling. Toxoplasma also suppresses TLR ligandstimulated IL-12 production from infected cells. Subsequently, I characterize the differences in recruitment and parasitization of cell types by different strains of Toxoplasma, demonstrating that the avirulent Types II and III strains lead to higher levels of CD11c-expressing DC at the infection site. Finally, I elucidate the cell populations targeted in the intestine and the mesenteric lymph nodes after oral inoculation. I find that in the mesenteric lymph nodes and Peyer’s patches, the cell types most strongly represented among infected cells are CD3+ or B220+ lymphocytes. However, the infection rate in these regions is highest in the cells expressing innate immune cell markers, such as Gr-1, CD11b, CD11c and 1A8/Ly6-G. Interestingly, infection in the lamina propria appears to be preferential for neutrophils, possibly indicating a role for neutrophils in dissemination of parasite during early oral infection.
dissertation or thesis