Turning it on and off: regulation of dendritic cell function in Toxoplasma gondii infection

Abstract

Because of its intrinsic virulence, Toxoplasma gondii induces a potent interleukin-12 (IL-12)-dependent cell-mediated immune response that shuts down the growth of the replicative tachyzoite stage, thus promoting host survival and successful transmission through predation. At the same time, this response must be tightly controlled to prevent lethality due to cytokine-mediated immunopathology. Evidence accumulated in recent years suggests that dendritic cells (DCs) play a major role in the initiation of IL-12-driven host resistance and that IL-12 synthesis by DCs is carefully regulated to avoid overproduction. In addition, this work has revealed a critical role for DCs in determining the highly polarized T-helper 1 (Th1)-type response triggered by the parasite. In this review, we summarize our current understanding of how DC function is initiated by Toxoplasma and how parasite-primed DCs drive Th1 effector choice. In addition, we discuss recent findings concerning the pathways responsible for endogenous regulation of DC IL-12 production during T. gondii infection.