IL-6 signaling SOCS critical for IL-12 host response to Toxoplasma gondii

SOCS are a family of proteins that play an important role in the negative regulation of the cytokine-JAK-STAT pathway. Socs3 deletion results in prolonged IL-6 signaling measured by STAT3 phosphorylation. A role for STAT3 and SOCS3 in the context of Toxoplasma gondii infection is of particular importance, because STAT3 appears to be a key target of T. gondii virulence factors. By utilizing LysM-cre Socs3 ^fl/fl mice, the Hunter laboratory recently established that macrophage-specific SOCS3 knockout mice have enhanced susceptibility to infection with T. gondii. The authors demonstrated that lack of SOCS3-mediated control of IL-6 signaling results in acute susceptibility to T. gondii due to impaired IL-12 production by inflammatory monocytes, macrophages and neutrophils. This article further explores these findings and their implications in the field of host resistance to microbial pathogens.