Inflammasomes are multiprotein complexes that assemble in response to infection or tissue damage to activate caspase-1 and induce the secretion of interleukin 1β (IL-1β) and IL-18. In Science, Shenoy et al. show that GBP5 is specifically required for assembly of the NLRP3 inflammasome in human and mouse macrophages in response to live bacteria and soluble agents but not in response to crystalline agents. GBP5 is a member of a family of guanylate-binding proteins with recently identified immunological functions, and its expression is optimally induced by stimulation with lipopolysaccharide plus interferon-γ. GBP5 directly interacts with NLRP3 and undergoes tetramerization in a GTPase-independent manner. The GBP5 tetramer promotes oligomerization of the adaptor ASC via its interaction with NLRP3, which suggests that this newly identified inflammasome component can coordinate the modular assembly requirements of the inflammasome.

Science 27, 481–485 (2012)