A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling

Renle Chang^#^{1 2 3}, Jiejie Sun^#^{4 5 6}, Jinyuan Leng^{1 2 3}, Zihan Wang^{1 2 3}, Shuyi Mu^{1 2 3}, Yinan Li^{1 2 3}, Jie Wang^{1 2 3}, Linsheng Song^{7 8 9}

Affiliations

¹ Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China.
² Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, China.
³ Dalian Key Laboratory of Aquatic Animal Diseases Prevention and Control, Dalian Ocean University, Dalian, China.
⁴ Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China. sunjiejie@dlou.edu.cn.
⁵ Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, China. sunjiejie@dlou.edu.cn.
⁶ Dalian Key Laboratory of Aquatic Animal Diseases Prevention and Control, Dalian Ocean University, Dalian, China. sunjiejie@dlou.edu.cn.
⁷ Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China. lshsong@dlou.edu.cn.
⁸ Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, China. lshsong@dlou.edu.cn.
⁹ Dalian Key Laboratory of Aquatic Animal Diseases Prevention and Control, Dalian Ocean University, Dalian, China. lshsong@dlou.edu.cn.

^# Contributed equally.

PMID: 40442231
PMCID: PMC12122919
DOI: 10.1038/s42003-025-08290-7

Abstract

In the present study, a new type of Caspase-1 homolog is identified from Crassostrea gigas (defined as CgCas1-2D). It is composed of 2×DSRM-CASc domain and has closer evolutionary relationship with mammalian Caspase-1s. The mRNA expressions of CgCas1-2D increase significantly after Vibrio splendidus or LPS stimulation. Recombinant CgCas1-2D and its 2×DSRM and CASc domains all bind various PAMPs and bacteria. rCgCas1-2D shows the highest binding activity to human Caspase-1 substrate. Upon recognizing bacteria, CgCas1-2D co-localizes and interacts with CgGSDME, while it has no cleavage activity to CgGSDME. CgCas1-2D inhibits the histone methylation and acetylation levels and CgNF-κB/Rel nuclear translocation mediated by CgGSDME. In addition, CgCas1-2D suppresses the mRNA expression levels of cytokines mediated by GSDME-NF-κB/Rel axis. The results demonstrate that a new type of anti-inflammatory Caspase-1 identified from oyster upon recognizing various bacteria interacts with GSDME to inhibit the histone modification and NF-κB signaling to suppress the inflammation.

Commun Biol . 2025 May 29;8(1):827.doi: 10.1038/s42003-025-08290-7. (IF:5.2).

A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling

Abstract

近期文章