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.

第 3 组先天淋巴细胞 (ILC3) 产生白细胞介素 (IL)-22，并与肠道中的其他细胞协调，增强宿主对细菌感染的免疫力。然而，ILC3 在引起人类食源性肠炎的肠沙门氏菌鼠伤寒沙门氏菌（ S. Typhimurium）感染中的作用仍然难以捉摸。在这里我们证明S .鼠伤寒菌利用 ILC3 产生的 IL-22 来促进其对小鼠的感染。具体来说， S .鼠伤寒杆菌通过激活抗原呈递细胞 (APC) 中的 TLR5-MyD88-IL-23 信号通路来分泌鞭毛蛋白，选择性增强 ILC3（而非 T 细胞）产生 IL-22。删除小鼠中的 ILC3 而不是 T 细胞可以更好地控制金黄色葡萄球菌。鼠伤寒感染。我们还表明S .鼠伤寒菌可直接侵入 ILC3，并独立于鞭毛蛋白引起 caspase-1 介导的 ILC3 焦亡。小鼠中Casp1的基因消除导致 ILC3 存活率和 IL-22 产量增加，并增强S .鼠伤寒感染。总的来说，我们的数据表明了针对S 的关键宿主防御机制。鼠伤寒感染通过诱导 ILC3 死亡来限制细胞内细菌并减少 IL-22 的产生。