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》。

据研究人员介绍，鸟苷三磷酸酶（GTPase）Rab32协调细胞内的宿主防御机制，从而限制囊泡内病原体（如沙门氏菌）的复制。

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

Issue&Volume: 2020/07/24

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.

DOI: 10.1126/science.aaz1333

Source: https://science.sciencemag.org/content/369/6502/450