Meixin Chen, Hui Sun, Maikel Boot, Lin Shao, Shu-Jung Chang, Weiwei Wang, Tukiet T Lam, Maria Lara-Tejero, E Hesper Rego, Jorge E Galán
Science (New York, N.Y.) 2020 Jul 24The 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. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Meixin Chen, Hui Sun, Maikel Boot, Lin Shao, Shu-Jung Chang, Weiwei Wang, Tukiet T Lam, Maria Lara-Tejero, E Hesper Rego, Jorge E Galán. Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella. Science (New York, N.Y.). 2020 Jul 24;369(6502):450-455
PMID: 32703879
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