Group 3 innate lymphoid cell pyroptosis represents a host defence mechanism against Salmonella infection

Group 3 innate lymphoid cells (ILC3s) produce interleukin (IL)-22 and coordinate with other cells in the gut to mount productive host immunity against bacterial infection. However, the role of ILC3s in Salmonella enterica serovar Typhimurium ( S . Typhimurium) infection, which causes foodborne enteritis in humans, remains elusive. Here we show that S . Typhimurium exploits ILC3-produced IL-22 to promote its infection in mice. Specifically, S . Typhimurium secretes flagellin through activation of the TLR5-MyD88-IL-23 signalling pathway in antigen presenting cells (APCs) to selectively enhance IL-22 production by ILC3s, but not T cells. Deletion of ILC3s but not T cells in mice leads to better control of S . Typhimurium infection. We also show that S . Typhimurium can directly invade ILC3s and cause caspase-1-mediated ILC3 pyroptosis independently of flagellin. Genetic ablation of Casp1 in mice leads to increased ILC3 survival and IL-22 production, and enhanced S . Typhimurium infection. Collectively, our data suggest a key host defence mechanism against S . Typhimurium infection via induction of ILC3 death to limit intracellular bacteria and reduce IL-22 production.