美国耶鲁大学医学院的Jorge E. Galán小组的最新工作表明，衣康酸是Rab GTPase细胞自主宿主防御途径的效应子，可抵御沙门氏菌感染。该研究于2020年7月24日发表于《科学》。
Author: 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
Abstract: 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.