Coral gasdermin triggers pyroptosis

Area of Science:

• Immunology
• Marine Biology
• Cell Biology

Background:

• Gasdermins are critical effectors of pyroptosis, a pro-inflammatory programmed cell death pathway.
• Pyroptosis has been exclusively studied in vertebrates, leaving its presence and function in invertebrates unexplored.

Purpose of the Study:

• To investigate the presence and function of gasdermin homologs in invertebrates.
• To determine the role of gasdermin E (GSDME) in coral immunity and response to bacterial infection.

Main Methods:

• Identification and characterization of gasdermin E (GSDME) homologs in coral species.
• In vitro assays involving caspase-mediated cleavage of coral GSDME and pyroptosis induction in human cells.
• Experimental infection of corals with *Vibrio coralliilyticus* and assessment of caspase activity and GSDME cleavage.

Main Results:

• Coral GSDME homologs were identified and shown to be cleaved by caspase 3, generating active N-terminal fragments.
• Coexpression of coral GSDME and caspase 3 induced pyroptosis in human cells.
• Infection with *Vibrio coralliilyticus* led to increased caspase 3 activity and GSDME cleavage in corals, with caspase inhibition protecting against necrotic death.

Conclusions:

• Functional gasdermin proteins exist in invertebrates, specifically in corals.
• Coral GSDME plays a crucial role in mediating necrotic cell death in response to bacterial pathogens.
• The findings suggest that pyroptosis mediation by gasdermins is an evolutionarily conserved mechanism.