Caspase‐4 mediates non‐canonical activation of the NLRP3 inflammasome in human myeloid cells
Citations Over TimeTop 10% of 2015 papers
Abstract
Inflammasome activation culminates in activation of caspase-1, which leads to the maturation and subsequent release of cytokines of the interleukin 1 (IL-1) family and results in a particular form of cell death known as pyroptosis. In addition, in the murine system, a so-called non-canonical inflammasome involving caspase-11 has been described that directly responds to cytosolic LPS. Here, we show that the human monocytic cell line THP1 activates the inflammasome in response to cytosolic LPS in a TLR4-independent fashion. This response is mediated by caspase-4 and accompanied by caspase-1 activation, pyroptosis, and IL-1β maturation. In addition to caspase-4, efficient IL-1β conversion upon intracellular LPS delivery relies on potassium efflux, NLRP3, ASC, and caspase-1, indicating that although caspase-4 activation alone is sufficient to induce pyroptosis, this process depends on the NLRP3 inflammasome activation to drive IL-1β maturation. Altogether, this study provides evidence for the presence of a non-canonical inflammasome in humans and its dependence on caspase-4.
Related Papers
- → The zebrafish NLRP3 inflammasome has functional roles in ASC-dependent interleukin-1β maturation and gasdermin E–mediated pyroptosis(2020)98 cited
- → Pyrin Domain (PYD)-containing Inflammasome in Innate Immunity(2011)19 cited
- → New progress on the activation mechanisms of NOD-like receptor, pyrin domain-containing 3 inflammasome(2015)
- Pyrin Domain (PYD)-containing Inflammasome in Innate Immunity(2011)