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Dual function of a turbot inflammatory caspase in mediating both canonical and non-canonical inflammasome activation.
- Source :
-
Developmental and comparative immunology [Dev Comp Immunol] 2021 Aug; Vol. 121, pp. 104078. Date of Electronic Publication: 2021 Mar 29. - Publication Year :
- 2021
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Abstract
- Host protective inflammatory caspase activity must be tightly regulated to prevent pathogens infection, however, the inflammatory caspase-engaged inflammasome activation in teleost fish remains largely unknown. In this study, we reveal a bifurcated evolutionary role of the inflammatory caspase in mediating both non-canonical and canonical inflammasome pathways in teleost fish. Through characterization of a unique inflammatory SmCaspase from the teleost Scophthalmus maximus (turbot), we found it can directly recognize cytosolic lipopolysaccharide (LPS) via its N-terminal CARD domain, resulting in caspase-5-like proteolytic enzyme activity-mediated pyroptosis in Turbot Muscle Fibroblasts. Interestingly, we also found that this inflammatory caspase can be recruited to SmNLRP3-SmASC to form the NLRP3 inflammasome complex, engaging the SmIL-1β release in Head Kidney-derived Macrophages. Consequently, the SmCaspase activation can recognize and cleave the SmGSDMEb to release its N-terminal domain, mediating both pyroptosis and bactericidal activities. Furthermore, the SmCaspase-SmGSDMEb axis-gated pyroptosis governs the bacterial clearance and epithelial desquamation in fish gill filaments in vivo. To our knowledge, this study is the first to identify an inflammatory caspase acting as a central coordinator in NLRP3 inflammasome, as well as a cytosolic LPS receptor; thus uncovering a previously unrecognized function of inflammatory caspase in turbot innate immunity.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Caspase Activation and Recruitment Domain genetics
Caspases genetics
Computational Biology
Edwardsiella immunology
Fish Proteins genetics
Flatfishes genetics
Flatfishes metabolism
Flatfishes microbiology
HEK293 Cells
HeLa Cells
Head Kidney cytology
Head Kidney immunology
Humans
Immunity, Innate
Inflammasomes metabolism
Lipopolysaccharides immunology
Macrophages immunology
Membrane Proteins metabolism
NLR Family, Pyrin Domain-Containing 3 Protein immunology
Phylogeny
Pyroptosis immunology
Caspases metabolism
Fish Proteins metabolism
Flatfishes immunology
Inflammasomes immunology
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0089
- Volume :
- 121
- Database :
- MEDLINE
- Journal :
- Developmental and comparative immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33794278
- Full Text :
- https://doi.org/10.1016/j.dci.2021.104078