How did we get here? Insights into mechanisms of immunity-related GTPase targeting to intracellular pathogens.

Journal Article (Journal Article;Review)

The cytokine gamma-interferon activates cell-autonomous immunity against intracellular bacterial and protozoan pathogens by inducing a slew of antimicrobial proteins, some of which hinge upon immunity-related GTPases (IRGs) for their function. Three regulatory IRG clade M (Irgm) proteins chaperone about approximately 20 effector IRGs (GKS IRGs) to localize to pathogen-containing vacuoles (PVs) within mouse cells, initiating a cascade that results in PV elimination and killing of PV-resident pathogens. However, the mechanisms that allow IRGs to identify and traffic specifically to 'non-self' PVs have remained elusive. Integrating recent findings demonstrating direct interactions between GKS IRGs and lipids with previous work, we propose that three attributes mark PVs as GKS IRG targets: the absence of membrane-bound Irgm proteins, Atg8 lipidation, and the presence of specific lipid species. Combinatorial recognition of these three distinct signals may have evolved as a mechanism to ensure safe delivery of potent host antimicrobial effectors exclusively to PVs.

Full Text

Duke Authors

Cited Authors

  • Dockterman, J; Coers, J

Published Date

  • October 2022

Published In

Volume / Issue

  • 69 /

Start / End Page

  • 102189 -

PubMed ID

  • 35963099

Electronic International Standard Serial Number (EISSN)

  • 1879-0364

Digital Object Identifier (DOI)

  • 10.1016/j.mib.2022.102189

Language

  • eng

Conference Location

  • England