Mechanisms and functions of guanylate ‐binding proteins and related interferon‐inducible GTPases: roles in intracellular lysis of pathogens

Abstract
Guanylate‐binding proteins (GBPs) are a group interferon‐inducible GTPases within the constellation of the dynamin GTPase superfamily. These proteins restrict the replication of intracellular pathogens in both immune and non‐immune cells. GBPs and their related family members Immunity‐related GTPases (IRGs) target and lyse the membrane of the pathogen‐containing vacuole, destroying the residential niche of vacuolar protozoal and bacterial pathogens. They also prevent virion infectivity and target replication complexes of RNA viruses. The exciting concept that GBPs and IRGs can directly target the membrane of bacteria and protozoa has emerged. Rupture and lysis of the pathogen membrane mediates liberation of concealed microbial ligands for activation of innate immune sensing pathways and the inflammasome. Further studies have demonstrated a capacity of GBPs to recruit additional antimicrobial factors, highlighting the complexity of the molecular mechanisms involved in pathogen killing. In this mini‐review, we discuss recent advances describing the localization and functions of GBPs on the host and pathogen membrane. We also highlight unresolved questions related to the regulation of GBPs in cell‐autonomous immunity to intracellular pathogens.

Source: Cellular Microbiology - October 1, 2017 Category: Microbiology Authors: Chinh C. Ngo, Si Ming Man Tags: MICROREVIEW Source Type: research