A human homolog of SIR2 antiphage proteins mediates immunity via the Toll-like receptor pathway

• 成果类型: Article
• 署名作者: Bonhomme, Delphine; Vaysset, Hugo; Ednacot, Eirene Marie Q.; Rodrigues, Vasco; Salloum, Yazan; Cury, Jean; Wang, Anny; Benchetrit, Axel; Affaticati, Pierre; Trejo, Veronica Hernandez; Vittot, Paul; Bories, Charlie; Cornec, Alexis; Levraud, Jean-Pierre; Hernandez, Pedro P.; Benaroch, Philippe; Morehouse, Benjamin R.; Bernheim, Aude; Poirier, Enzo Z.
• 署名单位: Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Universite Paris Saclay; AgroParisTech; University of California System; University of California Irvine; University of California System; University of California Irvine; Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); CNRS - National Institute for Biology (INSB); Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Universite Paris Cite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); University of California System; University of California Irvine; University of California System; University of California Irvine
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8266
• DOI: 10.1126/science.adr8536
• 发表日期: 2025-07-24
• 关键词: pattern-recognition receptors; antiviral immunity; structural basis; bacterial; activation; mechanism; crispr

摘要

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.