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

  • Commun Biol. 2025 May 29;8(1):827. doi: 10.1038/s42003-025-08290-7.
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. [email protected].
  • 5. Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, China. [email protected].
  • 6. Dalian Key Laboratory of Aquatic Animal Diseases Prevention and Control, Dalian Ocean University, Dalian, China. [email protected].
  • 7. Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China. [email protected].
  • 8. Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, China. [email protected].
  • 9. Dalian Key Laboratory of Aquatic Animal Diseases Prevention and Control, Dalian Ocean University, Dalian, China. [email protected].
  • # Contributed equally.
PMID: 40442231 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.

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