Sensing of invading pathogens by GBPs: At the crossroads between cell-autonomous and innate immunity

J Leukoc Biol. 2018 Oct;104(4):729-735. doi: 10.1002/JLB.4MR0118-038R. Epub 2018 Jul 18.

Abstract

Guanylate-binding proteins (GBPs) are conserved family of IFN-inducible GTPases that play an important role in the host immunity against bacterial, viral, and protozoan pathogens. GBPs protect the host by associating with intracellular microbes, their vacuolar niche or, in the case of viruses, with their replication complex. This association results in a restriction of the respective pathogen, yet the exact molecular mechanisms of the antimicrobial functions of GBPs are still unclear. Recent work has linked the GBPs with the activation of inflammasomes, multi-protein complexes that assemble upon recognition of pathogen- or host-derived signals and that drive the release of cytokines and host cell death. Here, we will focus on the most recent findings that have started to unravel the manifold restriction mechanism controlled by GBPs in mouse and human cells, and that shed light on the molecular cues that control GBP recruitment to bacterial membranes.

Keywords: Guanylate-binding proteins; caspase-11; inflammasomes; intracellular pathogens.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacterial Infections / enzymology
  • Bacterial Infections / immunology
  • Caspases / physiology
  • Cell Membrane / metabolism
  • Cytokines / metabolism
  • GTP-Binding Proteins / physiology*
  • Humans
  • Immunity, Innate*
  • Infections / enzymology
  • Infections / immunology*
  • Inflammasomes / immunology
  • Lipopolysaccharides / metabolism
  • Mammals / immunology
  • Mice
  • Parasitic Diseases / enzymology
  • Parasitic Diseases / immunology
  • Protein Transport
  • Protozoan Infections / enzymology
  • Protozoan Infections / immunology
  • Virus Diseases / enzymology
  • Virus Diseases / immunology

Substances

  • Cytokines
  • Inflammasomes
  • Lipopolysaccharides
  • Caspases
  • caspase 11, human
  • GTP-Binding Proteins