A human homolog of SIR2 antiphage proteins mediates immunity via the Toll-like receptor pathway
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.
Authors
- Pierre Affaticati (ORCID: https://orcid.org/0000-0001-9872-395X)
- Veronica Hernandez-Trejo (ORCID: https://orcid.org/0000-0003-2419-9600)
- Aude Bernheim (ORCID: https://orcid.org/0000-0003-0212-777X)
- Pedro P. Hernández (ORCID: https://orcid.org/0000-0002-2873-4298)
- Angela S. Wang
- Jean‐Pierre Levraud (ORCID: https://orcid.org/0000-0001-6775-2416)
- Yazan Salloum (ORCID: https://orcid.org/0009-0005-5181-4666)
- Enzo Z. Poirier (ORCID: https://orcid.org/0000-0001-9795-2144)
- Delphine Bonhomme (ORCID: https://orcid.org/0000-0002-3590-534X)
- Benjamin R. Morehouse (ORCID: https://orcid.org/0000-0003-3352-5463)
- Philippe Benaroch (ORCID: https://orcid.org/0000-0002-2655-0129)
- Vasco Rodrigues (ORCID: https://orcid.org/0000-0002-6014-321X)
- Avraham Ben‐Chetrit
- Jean Cury (ORCID: https://orcid.org/0000-0002-6462-8783)
- Alexis Cornec
- Hugo Vaysset (ORCID: https://orcid.org/0009-0007-3134-1966)
- Eirene Marie Q. Ednacot (ORCID: https://orcid.org/0009-0005-5305-3936)
- Charlie Bories (ORCID: https://orcid.org/0009-0001-5348-8762)
- Paul Vittot
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- University of California, Irvine (US)
- Université Paris Cité (FR)
- AgroParisTech (FR)
- Université Paris Sciences et Lettres (FR)
- Université Paris-Saclay (FR)
- Institut des Neurosciences Paris-Saclay (FR)
- Immunité et Cancer (FR)
- Irvine University (US)
- Génétique et biologie du développement (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Science
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1126/science.adr8536
- Citations
- 8
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 10.83