期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 45, 期 10, 页码 2911-2917出版社
WILEY
DOI: 10.1002/eji.201545523
关键词
Caspase-4; Myeloid cells; NLRP3; Non-canonical inflammasome
类别
资金
- German Research Foundation [SFB704, SFB670]
- European Research Council [ERC-2009-StG 243046]
- German National Academic Foundation
- BONFOR program of the University Hospital Bonn
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-1 maturation. In addition to caspase-4, efficient IL-1 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-1 maturation. Altogether, this study provides evidence for the presence of a non-canonical inflammasome in humans and its dependence on caspase-4.
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