University of Pittsburgh Department of Biological Sciences Presents:
Friday Noon Seminar Series 2017-2018
Graduate Student: Rachel Coombs
Identifying the molecular mechanisms underlying the broad host range of T. gondii T. gondii is a notoriously promiscuous parasite capable of infecting mammals indiscriminately while its close relative N. caninum cannot. Mechanisms driving this broad host range are poorly understood. We have shown that T. gondii and N. caninum grow similarly in mice during the first 24h, but post-infection only N. caninum induce a potent and “immediate” Interferon-gamma (IFNγ) response within 4h that quickly controls N. caninum. Using immune-deficient mice I identified two distinct immune responses sufficient to control N. caninum infections. First we identified a MyD88/IFNg-dependent response capable of controlling N. caninum within 24h. In the absence of MyD88, a second IFNg-mediated response independent of IL-12 is also sufficient to control N. caninum within days. I have found that acute control of N. caninum infection does not require TLR3 or TRIF signaling, and type-I interferons (IFNa/b) are not detected in N. caninum infected mice. These data show that IFNγ, but not IFNa/b signaling, is necessary for N. caninum control in mice. To identify the molecule responsible for immediate IFNγ induction, I compared IFNγ production in mice injected with different N. caninum tachyzoite preparations. I have found that N. caninum soluble tachyzoite antigen (NcSTAg) induces IFNγ when injected into mice, and insoluble fractions do not. Treatment of NcSTAg with proteinase-K (PK) abolishes IFNγ induction in vivo. My data suggests that soluble proteins in N. caninum tachyzoite lysate are responsible for immediate induction of IFNγ in mouse infections.
Friday, January 5, 2017
A219B Langley Hall
12:00 PM Seminar