A critical role for SOCS3 in innate resistance to Toxoplasma gondii.

ABSTRACT: The innate and adaptive immune responses that confer resistance to the intracellular pathogen Toxoplasma gondii critically depend on IL-12 production, which drives interferon-γ (IFN-γ) expression. Certain cytokines can activate STAT3 and limit IL-12 production to prevent infection-associated immune pathology, but T. gondii also directly activates STAT3 to evade host immunity. We show that suppressor of cytokine signaling molecule 3 (SOCS3), a target of STAT3 that limits signaling by the pleiotropic cytokine IL-6, is upregulated in response to infection but is dispensable for the immune-inhibitory effects of T. gondii. Unexpectedly, mice with targeted deletion of SOCS3 in macrophages and neutrophils have reduced IL-12 responses and succumb to toxoplasmosis. Anti-IL-6 administration or IL-12

SUBMITTER: Whitmarsh RJ 

PROVIDER: S-EPMC3176442 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature