TRIM32 Reduced the Recruitment of Innate Immune Cells and the Killing Capacity of Listeria monocytogenes by Inhibiting Secretion of Chemokines

Abstract

Abstract Listeria monocytogenes (Lm) is a facultative, intracellular Gram-positive pathogenic bacterium that causes sepsis, a condition characterized by persistent excessive inflammation and organ dysfunction. However, the pathogenesis of Lm-induced sepsis is unknown. In this research, we discovered that TRIM32 is required for innate immune regulation during Lm infection. Trim32 deficiency remarkably reduced bacteremia and proinflammatory cytokine secretion in mice with severe Lm infection, preventing sepsis. Trim32-/- mice had a lower bacterial burden after Lm infection and survived significantly longer than wild-type (WT) mice, as well as lower serum levels of inflammatory cytokines TNF-α, IL-6, IL-18, IL-12p70, IFN-β, and IFN-γ at 1 day post infection (dpi) compared to WT mice. On the other hand, the chemokines CXCL1, CCL-2, CCL-7, and CCL-5 were increased at 3 dpi in Trim32-/- mice compared to WT mice, implying increased recruitment of neutrophils and macrophages to clear Lm. Furthermore, Trim32-/- mice also produced more macrophage-associated iNOS. Collectively, our findings suggest that TRIM32 reduces innate immune cells recruitment and Lm killing ability by inhibiting chemokines secretion.