PUBLICATION
A human homolog of SIR2 antiphage proteins mediates immunity via the Toll-like receptor pathway
- Authors
- Bonhomme, D., Vaysset, H., Ednacot, E.M.Q., Rodrigues, V., Salloum, Y., Cury, J., Wang, A., Benchetrit, A., Affaticati, P., Trejo, V.H., Vittot, P., Bories, C., Cornec, A., Levraud, J.P., Hernández, P.P., Benaroch, P., Morehouse, B.R., Bernheim, A., Poirier, E.Z.
- ID
- ZDB-PUB-250725-4
- Date
- 2025
- Source
- Science (New York, N.Y.) 389: eadr8536eadr8536 (Journal)
- Registered Authors
- Affaticati, Pierre, Levraud, Jean-Pierre
- Keywords
- none
- MeSH Terms
-
- Herpes Simplex/immunology
- Protein Domains
- Signal Transduction
- Salmonella enterica/immunology
- Animals
- Sirtuins*/classification
- Sirtuins*/genetics
- Sirtuins*/metabolism
- Humans
- Genome
- Immunity, Innate*
- Phylogeny
- RAW 264.7 Cells
- Zebrafish/genetics
- Toll-Like Receptors*/metabolism
- Salmonella Infections/immunology
- Macrophages*/immunology
- Macrophages*/microbiology
- Macrophages*/virology
- Mice
- Herpesvirus 1, Human/immunology
- PubMed
- 40705877 Full text @ Science
Citation
Bonhomme, D., Vaysset, H., Ednacot, E.M.Q., Rodrigues, V., Salloum, Y., Cury, J., Wang, A., Benchetrit, A., Affaticati, P., Trejo, V.H., Vittot, P., Bories, C., Cornec, A., Levraud, J.P., Hernández, P.P., Benaroch, P., Morehouse, B.R., Bernheim, A., Poirier, E.Z. (2025) A human homolog of SIR2 antiphage proteins mediates immunity via the Toll-like receptor pathway. Science (New York, N.Y.). 389:eadr8536eadr8536.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping