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, Hernández Pedro P, Benaroch Philippe, Morehouse Benjamin R, Bernheim Aude, Poirier Enzo Z
Innate Immunity in Physiology and Cancer Team, Institut Curie, PSL Research University, INSERM U932, Paris, France.
Molecular Diversity of Microbes Lab, Institut Pasteur, Université Paris-Cité, CNRS UMR3525, Paris, France.
Science. 2025 Jul 24;389(6758):eadr8536. doi: 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.
哺乳动物免疫的关键参与者起源于细菌抗噬菌体系统。细菌和真核生物之间免疫系统保守性的全貌尚不清楚。在这里，我们表明存在于抗噬菌体系统中的沉默信息调节因子2（SIR2）蛋白结构域在真核生物先天免疫中发挥作用。我们鉴定出了SIRal，一种具有SIRim结构域（SIR2的亚型）的人类蛋白，它在动物先天免疫的Toll样受体途径中起关键作用，并能抵御细菌和病毒感染。含有SIRim结构域的蛋白质存在于19%的真核生物基因组中，包括斑马鱼，在斑马鱼中SIRal在炎症中发挥作用。这项工作开辟了关于真核生物SIRim蛋白的免疫作用以及SIRal在人类病理学中的作用的研究途径。
