Chen, MeixinMeixinChenSun, HuiHuiSunBoot, MaikelMaikelBootShao, LinLinShaoSHU-JUNG CHANGWang, WeiweiWeiweiWangLam, Tukiet T.Tukiet T.LamLara-Tejero, MariaMariaLara-TejeroRego, E. HesperE. HesperRegoGalán, Jorge E.Jorge E.Galán2024-01-102024-01-102020-07-2400368075https://scholars.lib.ntu.edu.tw/handle/123456789/638336The 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.enjournal article10.1126/science.aaz1333327038792-s2.0-85088532141https://api.elsevier.com/content/abstract/scopus_id/85088532141