| First Author | Chen M | Year | 2020 |
| Journal | Science | Volume | 369 |
| Issue | 6502 | Pages | 450-455 |
| PubMed ID | 32703879 | Mgi Jnum | J:297588 |
| Mgi Id | MGI:6449447 | Doi | 10.1126/science.aaz1333 |
| Citation | Chen M, et al. (2020) Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella. Science 369(6502):450-455 |
| abstractText | 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. |
