GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals

Abstract

Generating Inflammasomes Inflammasomes are large, multiprotein complexes that assemble in response to infection that are also involved in the pathogenesis of a variety of other diseases, including type 2 diabetes and atherosclerosis. The assembly of the inflammasome triggers an inflammatory cascade that results in the activation of caspase-1 and production of the cytokines interleukin-1 and -18. Very little, however, is known about the specific signals that trigger inflammasome assembly. Shenoy et al. (p. 481, published online 29 March; see the Perspective by Caffrey and Fitzgerald ) now show that guanylate binding protein 5 (GBP5) promotes the assembly of the NLRP3-containing inflammasome in response to certain activation signals, such as pathogenic bacteria and adenosine triphosphate, but not others, like crystalline stimuli. Mice deficient in GBP5 exhibited impaired caspase-1 activation and production of cytokines. NLRP3 inflammasome–dependent responses to pathogenic bacteria and inflammatory stimuli were also impaired in mice lacking GBP5.