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Published in Science - 24 Jul 2025

Delphine Bonhomme, Hugo Vaysset, Eirene Marie Q. Ednacot, Vasco Rodrigues, Yazan Salloum, Jean Cury, Anny Wang, Axel Benchetrit, Pierre Affaticati, Veronica Hernandez Trejo, Paul Vittot, Charlie Bories, Alexis Cornec, Jean-Pierre Levraud, Pedro Hernández, Philippe Benaroch, Benjamin Morehouse, Aude Bernheim, Enzo Poirier

Link to Pubmed [PMID] – 40705877

Link to HAL – hal-05232966

Link to DOI – 10.1126/science.adr8536

Science, 2025, 389 (6758), pp.eadr8536. ⟨10.1126/science.adr8536⟩

Key actors of mammalian immunity originated from bacterial antiphage systems. The full extent of immune system conservation between bacteria and eukaryotes is unknown. Here, we show that the silent information regulator 2 (SIR2) protein domain, present in antiphage systems, plays a role in eukaryotic innate immunity. We identified SIRal, a human protein with a SIRim domain (subtype of SIR2) that plays a pivotal role in the animal Toll-like receptor pathway of innate immunity and protects against bacterial and viral infections. Proteins containing a SIRim domain are found across 19% of eukaryotic genomes, including zebrafish, where SIRal plays a role in inflammation. This work opens up avenues of research on the immune role of eukaryotic SIRim proteins as well as on the involvement of SIRal in human pathology.