Macrophages orchestrate elimination of from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ.

Bacteria of the genus replicate in intestinal epithelial cells and cause shigellosis, a severe diarrheal disease that resolves spontaneously in most healthy individuals. During shigellosis, neutrophils are abundantly recruited to the gut, and have long been thought to be central to control and pathogenesis. However, how shigellosis resolves remains poorly understood due to the longstanding lack of a tractable and physiological animal model. Here, using our newly developed mouse model of shigellosis, we unexpectedly find no major role for neutrophils in limiting or in disease pathogenesis. Instead, we uncover an essential role for macrophages in the host control of . Macrophages respond to via TLRs to produce IL-12, which then induces IFN-γ, a cytokine that is essential to control replication in intestinal epithelial cells. Collectively, our findings reshape our understanding of the innate immune response to .