Interferon-inducible Guanylate-Binding Proteins at the Interface of Cell-Autonomous Immunity and Inflammasome Activation

J Leukoc Biol. 2017 Jan;101(1):143-150. doi: 10.1189/jlb.4MR0516-223R. Epub 2016 Jul 14.

Abstract

Guanylate-binding proteins (GBPs) are essential components of cell-autonomous immunity. In response to IFN signaling, GBPs are expressed in the cytoplasm of immune and nonimmune cells, where they unleash their antimicrobial activity toward intracellular bacteria, viruses, and parasites. Recent studies have revealed that GBPs are essential for mediating activation of the caspase-1 inflammasome in response to the gram-negative bacteria Salmonella enterica serovar Typhimurium, Francisella novicida, Chlamydia muridarum, Chlamydia trachomatis, Legionella pneumophila, Vibrio cholerae, Enterobacter cloacae, and Citrobacter koseri During infection with vacuolar-restricted gram-negative bacteria, GBPs disrupt the vacuolar membrane to ensure liberation of LPS for cytoplasmic detection by caspase-11 and the noncanonical NLRP3 inflammasome. In response to certain cytosolic bacteria, GBPs liberate microbial DNA for activation of the DNA-sensing AIM2 inflammasome. GBPs also promote the recruitment of antimicrobial proteins, including NADPH oxidase subunits and autophagy-associated proteins to the Mycobacterium-containing vacuole to mediate intracellular bacterial killing. Here, we provide an overview on the emerging relationship between GBPs and activation of the inflammasome in innate immunity to microbial pathogens.

Keywords: GBPs; bacteria; caspase-1; caspase-11; pyroptosis; viruses.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Communicable Diseases / microbiology
  • Communicable Diseases / parasitology
  • Communicable Diseases / virology
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Immunity, Cellular*
  • Inflammasomes / metabolism*
  • Interferons / metabolism*
  • Models, Biological

Substances

  • Inflammasomes
  • Interferons
  • GTP-Binding Proteins