Interferon-induced guanylate-binding proteins in inflammasome activation and host defense.
Traditional views of the inflammasome highlight the assembly of pre-existing core components shortly after infection or tissue damage. Emerging work, however, suggests that the inflammasome machinery is also subject to 'tunable' or inducible signals that might accelerate its autocatalytic properties and dictate where inflammasome assembly takes place in the cell. Many of these signals operate downstream of interferon receptors to elicit inflammasome regulators, including a new family of interferon-induced GTPases called 'guanylate-binding proteins' (GBPs). Here we investigate the critical roles of interferon-induced GBPs in directing inflammasome subtype-specific responses and their consequences for cell-autonomous immunity to a wide variety of microbial pathogens. We discuss emerging mechanisms of action and the potential effect of these GBPs on predisposition to sepsis and other infectious or inflammatory diseases.
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.|Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
Bae-Hoon
BH
Kim
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
Jonathan D
JD
Chee
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
Clinton J
CJ
Bradfield
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
Eui-Soon
ES
Park
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
Pradeep
P
Kumar
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.|Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.|Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
John D
JD
MacMicking
D000818:Animals; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D019204:GTP-Binding Proteins / Q000145:classification / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007239:Infections / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007372:Interferons / Q000276:immunology* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology / Q000502:physiology; D051379:Mice; D018448:Models, Immunological; D010802:Phylogeny; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology / Q000502:physiology
C490287:GBP1 protein, human; D058847:Inflammasomes; D007372:Interferons; D019204:GTP-Binding Proteins