TIR signaling activates caspase-like immunity in bacteria

• 成果类型: Article
• 署名作者: Rousset, Francois; Osterman, Ilya; Scherf, Tali; Falkovich, Alla H.; Leavitt, Azita; Amitai, Gil; Shir, Sapir; Malitsky, Sergey; Itkin, Maxim; Savidor, Alon; Sorek, Rotem
• 署名单位: Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Claude Bernard Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Ecole Normale Superieure de Lyon (ENS de LYON)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10729
• DOI: 10.1126/science.adu2262
• 发表日期: 2025-01-31
• 关键词: cell-death; receptors; cleavage; systems

摘要

Caspase family proteases and Toll/interleukin-1 receptor (TIR)-domain proteins have central roles in innate immunity and regulated cell death in humans. We describe a bacterial immune system comprising both a caspase-like protease and a TIR-domain protein. We found that the TIR protein, once it recognizes phage invasion, produces the previously unknown immune signaling molecule adenosine 5-diphosphate-cyclo[N7:1 '']-ribose (N7-cADPR). This molecule specifically activates the bacterial caspase-like protease, which then indiscriminately degrades cellular proteins to halt phage replication. The TIR-caspase defense system, which we denote as type IV Thoeris, is abundant in bacteria and efficiently protects against phage propagation. Our study highlights the diversity of TIR-produced immune signaling molecules and demonstrates that cell death regulated by proteases of the caspase family is an ancient mechanism of innate immunity.