Cell-mediated Immunity to Toxoplasma Gondii: Initiation, Regulation and Effector Function

Cell-mediated immune responses are essential for host control of intracellular infections. Toxoplasma gondii is a protozoan parasite that infects multiple vertebrate species and invades multiple cell types. Upon initial encounter with the immune system, the parasite rapidly induces production of the type-1 promoting cytokine IL-12 most likely from a subpopulation of dendritic cells. NK and T cells are then activated and triggered to synthesize IFN-gamma, the major mediator of host resistance during the acute and chronic phases of infection. During the acute phase, a concomitant IL-10 response dampens the systemic type-1 cytokine production and prevents lethal immunopathology. Cytokine (IFN-gamma und TNF-alpha) rather than cytotoxicity-based effector functions are more critical for protective immunity both during the acute and chronic phases of T. gondii infection. Both hemopoietic and non-hemopoietic cellular elements act as IFN-gamma and TNF-dependent effectors of host resistance. Type II iNOS-derived nitric oxide (NO) is required mainly for hemopoietic cell-derived effector cell activity in the central nervous system (CNS) during the chronic phase of infection. Nevertheless, in both the acute and chronic stages, IFN-gamma-dependent but iNOS-independent mechanism(s) play a major function in parasite control and their identification remains an important challenge for this field.