The guanosine triphosphatase (GTPase) Rab32 coordinates a cell-intrinsic host defense mechanism that restricts the replication of intravacuolar pathogens such as Salmonella. Here, we show that this mechanism requires aconitate decarboxylase 1 (IRG1), which synthesizes itaconate, a metabolite with antimicrobial activity. We find that Rab32 interacts with IRG1 on Salmonella infection and facilitates the delivery of itaconate to the Salmonella-containing vacuole. Mice defective in IRG1 rescued the virulence defect of a S. enterica serovar Typhimurium mutant specifically defective in its ability to counter the Rab32 defense mechanism. These studies provide a link between a metabolite produced in the mitochondria after stimulation of innate immune receptors and a cell-autonomous defense mechanism that restricts the replication of an intracellular bacterial pathogen.

鸟苷三磷酸酶 (GTPase) Rab32 协调一种细胞固有的宿主防御机制，该机制限制了沙门氏菌等液泡内病原体的复制。在这里，我们表明这种机制需要乌头酸脱羧酶 1 (IRG1)，它合成衣康酸，一种具有抗菌活性的代谢物。我们发现 Rab32 在沙门氏菌感染时与 IRG1 相互作用，并有助于将衣康酸输送到含沙门氏菌的液泡。IRG1 缺陷的小鼠挽救了S. enterica的毒力缺陷鼠伤寒血清型突变体在对抗 Rab32 防御机制的能力方面特别有缺陷。这些研究提供了在先天免疫受体刺激后线粒体中产生的代谢物与限制细胞内细菌病原体复制的细胞自主防御机制之间的联系。