In the study published in the journal Cellular & Molecular Immunology on August 17, 2023, entitled cFLIPs regulates alternative NLRP3 inflammasome activation in human monocytes, Prof. MENG Guangxun’s group at the Shanghai Institute of Immunity and Infection of the Chinese Academy of Sciences reported their new research.

The innate immune responses, including inflammasome activation, are paramount for host defense against pathogen infection. In contrast to canonical and noncanonical inflammasome activation, in this study, heat-killed gram-negative bacteria (HK bacteria) were identified as single-step stimulators of the NLRP3 inflammasome in human monocytes, and they caused a moderate amount of IL-1β to be released from cells. Time course experiments showed that this alternative inflammasome response was finished within a few hours.

Further analysis showed that the intrinsically limited NLRP3 inflammasome activation response was due to the negative regulation of caspase-8 by the short isoform of cFLIP (cFLIPs), which was activated by NF-κB. In contrast, overexpressed cFLIPS, but not overexpressed cFLIPL, inhibited the activation of caspase-8 and the release of IL-1β in response to HK bacteria infection in human monocytes.