Research ArticleInflammasomes

The signaling adaptor BCAP inhibits NLRP3 and NLRC4 inflammasome activation in macrophages through interactions with Flightless-1

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Science Signaling  14 May 2019:
Vol. 12, Issue 581, eaau0615
DOI: 10.1126/scisignal.aau0615

BCAPing inflammasome activation

The PI3K adaptor protein BCAP limits cellular responses to TLR stimulation and IL-1β. Using proteomics analysis, Carpentier et al. showed that BCAP interacted with Flightless-1 and its binding partner leucine-rich repeat Flightless-1–interacting protein 2 (LRRFIP2), which promoted an association between BCAP and the inflammasome component NLRP3. In macrophages, BCAP reduced the abundance of active caspase-1, maturation of the cytokine IL-1β, and cell death after exposure to the toxin nigericin or bacterial infection. Kinetic analyses determined that BCAP delayed recruitment of pro–caspase-1 to intracellular inflammasome foci and loss of BCAP promoted bacterial clearance in mice. These data identify a distinct role for this PI3K adaptor in preventing excessive, potentially harmful activation of NLRP3 and NLRC4 inflammasomes.