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Reviews & Commentaries
Caspase‐11 non‐canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage‐mediated inflammatory responses
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Abstract

Inflammatory responses mediated by macrophages are part of the innate immune system, whose role is to protect against invading pathogens. Lipopolysaccharide (LPS) found in the outer membrane of Gram‐negative bacteria stimulates an inflammatory response by macrophages. During the inflammatory response, extracellular LPS is recognized by Toll‐like receptor 4, one of the pattern recognition receptors that activates inflammatory signalling pathways and leads to the production of inflammatory mediators. The innate immune response is also triggered by intracellular inflammasomes, and inflammasome activation induces pyroptosis and the secretion of pro‐inflammatory cytokines such as interleukin‐1β (IL‐1β) and IL‐18 by macrophages. Cysteine‐aspartic protease (caspase)‐11 and the human orthologues caspase‐4/caspase‐5 were recently identified as components of the ‘non‐canonical inflammasome’ that senses intracellular LPS derived from Gram‐negative bacteria during macrophage‐mediated inflammatory responses. Direct recognition of intracellular LPS facilitates the rapid oligomerization of caspase‐11/4/5, which results in pyroptosis and the secretion of IL‐1β and IL‐18. LPS is released into the cytoplasm from Gram‐negative bacterium‐containing vacuoles by small interferon‐inducible guanylate‐binding proteins encoded on chromosome 3 (GBPchr3)‐mediated lysis of the vacuoles. In vivo studies have clearly shown that caspase‐11−/− mice are more resistant to endotoxic septic shock by excessive LPS challenge. Given the evidence, activation of caspase‐11 non‐canonical inflammasomes by intracellular LPS is distinct from canonical inflammasome activation and provides a new paradigm in macrophage‐mediated inflammatory responses.

Keywords : Gram‐negative bacteria,  inflammation,  intracellular lipopolysaccharide,  macrophage,  non‐canonical inflammasome

주소복사
논문정보   F1000선정
- 형식: Review Paper
- 게재일: 2017년 10월 (BRIC 등록일 2019-10-16)
- 연구진: 국내연구진태극기
- 분야: Immunology
- 추천: Faculty of 1000 Biology
- 추천사유: Weiss J: F1000Prime Recommendation of [Yi YS, Immunology 2017 152(2):207-217]. In F1000Prime, 20 Apr 2018; 10.3410/f.727799121.793545010
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