IFNs in host defence and parasite immune evasion during Toxoplasma gondii infections.

ABSTRACT

Interferons (IFNs) are a family of cytokines with diverse functions in host resistance to pathogens and in immune regulation. Type II IFN, i.e. IFN-γ, is widely recognized as a major mediator of resistance to intracellular pathogens, including the protozoan Toxoplasma gondii. More recently, IFN-α/ß, i.e. type I IFNs, and IFN-λ (type III IFN) have been identified to also play important roles during T. gondii infections. This parasite is a widespread pathogen of humans and animals, and it is a model organism to study cell-mediated immune responses to intracellular infection. Its success depends, among other factors, on the ability to counteract the IFN system, both at the level of IFN-mediated gene expression and at the level of IFN-regulated effector molecules. Here, I review recent advances in our understanding of the molecular mechanisms underlying IFN-mediated host resistance and immune regulation during T. gondii infections. I also discuss those mechanisms that T. gondii has evolved to efficiently evade IFN-mediated immunity. Knowledge of these fascinating host-parasite interactions and their underlying signalling machineries is crucial for a deeper understanding of the pathogenesis of toxoplasmosis, and it might also identify potential targets of parasite-directed or host-directed supportive therapies to combat the parasite more effectively.