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The endogenous glucocorticoid response plays a critical immunoregulatory role during Toxoplasma gondii infection by preventing T-cell-mediated lethality

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center



* FARE Award Winner


  • DG Kugler
  • PR Mittelstadt
  • JD Ashwell
  • A Sher
  • D Jankovic


Toxoplasma gondii is an intracellular protozoan parasite that triggers a highly polarized IL-12-dependent Th1 response required for control of pathogen replication. However, if left unregulated, this response can cause host-tissue damage and lead to mortality. We observed that, in addition to immunosuppressive cytokines (e.g. IL-10, IL-27), toxoplasma infection elicits an increased level of glucocorticoids (GC). GCs are steroid hormones that play an important role in glucose metabolism, but are also known to exert various immunomodulatory effects. To test the effect of endogenous GCs on the Th1 response during toxoplasma infection, we employed mice that selectively lack the expression of GC receptor (GR) in T cells. Unexpectedly, T. gondii-infected GRfl/fl LCK-cre animals displayed enhanced acute mortality despite effective parasite control. Moreover, the increased susceptibility was not due to deficient IFN-gamma or altered IL-12 production. To the contrary, T. gondii-infected GRfl/fl LCK-cre mice displayed an over-exuberant Th1 response with increased serum IFN-gamma and IL-10 levels. Furthermore, the expression of both IFN-gamma and IL-10 mRNA were increased in purified CD4+ T cells from infected GRfl/fl LCK-cre mice. Together, our results show that endogenous GCs play an essential, and non-redundant, regulatory role during T. gondii infection by dampening the effector Th1 response.

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