The loss-of-function of SOCS2 increases the inflammatory response to Staphylococcus aureus infection

Abstract

The involvement of suppressor of cytokine signaling (SOCS)2 in anti-infective bacterial immunity remains largely undetermined compared to other members of the SOCS family. We developed a mouse model expressing the loss of function R96C SOCS2 point mutation to characterize the response of macrophages to Staphylococcus aureus and its TLR-ligand derivatives. The model resumes observations of gigantism done in Socs2-/- mice. Stimulation of bone-marrow-derived macrophages with various TLR-2 ligands showed upregulation of the pro-inflammatory cytokines IL-6 and TNF- production only in cytokine-modulating environments that promote SOCS2 expression. Using this model, we showed that SOCS2 protein reduces STAT-5 phosphorylation in a short time frame upon TLR engagement. When SOCS2 is ablated, neutrophil and F4/80int Ly6C+ inflammatory macrophage recruitment, as well as IFN-{gamma} and IL-10 concentrations are significantly increased upon S. aureus peritoneal infection. By lowering the pro-inflammatory environment, SOCS2 favors better healing during a systemic infection caused by S. aureus.