期刊
SCIENCE
卷 369, 期 6502, 页码 450-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaz1333
关键词
-
资金
- CTSA from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) [UL1TR001863]
- NIH [R01AI114618, R01AI055472]
- Pew Biomedical Research Program
- Searle Scholars Program
- EMBO long-term fellowship
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据