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Interferon‐inducible guanylate‐binding proteins at the interface of cell‐autonomous immunity and inflammasome activation
Author(s) -
Man Si Ming,
Place David E.,
Kuriakose Teneema,
Kanneganti ThirumalaDevi
Publication year - 2017
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.4mr0516-223r
Subject(s) - biology , inflammasome , microbiology and biotechnology , immunity , innate immune system , interferon , lymphocyte activation , interface (matter) , immunology , immune system , t cell , biochemistry , inflammation , pulmonary surfactant , gibbs isotherm
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.