Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella

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.

Source: ScienceNOW - July 22, 2020 Category: Science Authors: Chen, M., Sun, H., Boot, M., Shao, L., Chang, S.-J., Wang, W., Lam, T. T., Lara-Tejero, M., Rego, E. H., Galan, J. E. Tags: Immunology, Microbiology reports Source Type: news