Cleavage of gasdermin by apoptotic caspases triggers pyroptosis restricting bacterial colonization in Hydra.
Dev Comp Immunol
; 155: 105139, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38325499
ABSTRACT
Gasdermin (GSDM) proteins, as the direct executors of pyroptosis, are structurally and functionally conserved among vertebrates and play crucial roles in host defense against infection, inflammation, and cancer. However, the origin of functional GSDMs remains elusive in the animal kingdom. Here, we found that functional GSDME homologs first appeared in the cnidarian. Moreover, these animal GSDME homologs share evolutionarily conserved apoptotic caspase cleavage sites. Thus, we verified the functional conservation of apoptotic caspase-GSDME cascade in Hydra, a representative species of cnidarian. Unlike vertebrate GSDME homologs, HyGSDME could be cleaved by four Hydra caspase homologs with caspase-3 activity at two sites. Furthermore, in vivo activation of Hydra caspases resulted in HyGSDME cleavage to induce pyroptosis, exacerbating injury and restricting bacterial burden, which protects Hydra from pathogen invasion. In conclusion, these results suggest that GSDME-dependent pyroptosis may be an ancient and conserved host defense mechanism, which may contribute to better understanding on the origin and evolution of GSDMs.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piroptose
/
Hydra
Limite:
Animals
Idioma:
En
Revista:
Dev Comp Immunol
Ano de publicação:
2024
Tipo de documento:
Article