GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals

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.