Spotted seabass Lateolabrax maculatus GSDMEa: a pyroptosis executor activated by CASP3/7 during bacterial infection

Xin Ding1, Yuan Chen2, Qingyue Wang1

  • 1State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture and Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China; University of Chinese Academy of Sciences, College of Marine Sciences, Qingdao, China.

Insights

Spotted seabass pyroptosis involves gasdermin E (GSDME) and caspases (CASP). Caspase-activated GSDME triggers pyroptosis, enhancing fish immunity against bacterial infections like Photobacterium damselae subsp. piscicida.

Area of Science:

  • Immunology
  • Cell Biology
  • Aquatic Animal Health

Background:

  • Pyroptosis is a key programmed cell death pathway crucial for host defense against bacterial pathogens.
  • Spotted seabass (Lateolabrax maculatus) aquaculture is significantly impacted by bacterial infections, particularly Photobacterium damselae subsp. piscicida (PDP).
  • The role of gasdermin in spotted seabass immunity and its activation mechanism during bacterial infection remain largely uncharacterized.

Purpose of the Study:

  • To identify and characterize gasdermin E (GSDME) and caspase (CASP) family members in spotted seabass.
  • To elucidate the mechanism of GSDME activation and its role in pyroptosis induction in spotted seabass.
  • To investigate the involvement of GSDME-mediated pyroptosis in spotted seabass immune response against PDP infection.

Main Methods:

  • Identification and cloning of GSDME and CASP genes from spotted seabass.
  • In vitro assays to assess CASP-mediated cleavage of GSDME and pyroptosis induction.
  • Quantitative analysis of gene and protein expression in fish tissues and macrophages following PDP challenge.
  • Assessment of pyroptotic cell death in response to bacterial infection.

Main Results:

  • Two spotted seabass GSDME genes (LmGSDMEa, LmGSDMEb) and three CASP genes (LmCASP3, LmCASP6, LmCASP7) were identified.
  • LmCASP3 and LmCASP7 specifically cleaved LmGSDMEa at site 262NTVD265, converting apoptosis into pyroptosis; LmGSDMEb did not induce pyroptosis.
  • PDP infection upregulated LmCASP3/7, LmGSDMEa, and pyroptosis-related cytokines in fish tissues and promoted pyroptotic cell death in spotted seabass macrophages.

Conclusions:

  • Spotted seabass possess a functional GSDMEa-mediated pyroptosis pathway activated by LmCASP3/7.
  • This pathway plays a significant role in the innate immune response of spotted seabass against bacterial pathogens like PDP.
  • The findings provide crucial insights into fish immunity and potential targets for disease control in aquaculture.

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