Toxoplasma gondii effector TgIST blocks type I interferon signaling to promote infection.

ABSTRACT: In contrast to the importance of type II interferon-? (IFN-?) in control of toxoplasmosis, the role of type I IFN is less clear. We demonstrate here that TgIST, a secreted effector previously implicated in blocking type II IFN-? signaling, also blocked IFN-? responses by inhibiting STAT1/STAT2-mediated transcription in infected cells. Consistent with a role for type I IFN in cell intrinsic control, ?Tgist mutants were more susceptible to growth inhibition by murine and human macrophages activated with IFN-?. Additionally, type I IFN was important for production of IFN-? by natural killer (NK) cells and recruitment of inflammatory monocytes at the site of infection. Mice lacking type I IFN receptors (Ifnar1-/-) showed increased mortality following infection with wild-type parasites and decreased virulence of ?Tgist parasites was restored in Ifnar1-/- mice. The findings highlight the importance of type I IFN in control of toxoplasmosis and illuminate a parasite mechanism to counteract the effects of both type I and II IFN-mediated host defenses.

SUBMITTER: Matta SK 

PROVIDER: S-EPMC6717281 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature