Abstract
Proteases of the caspase family, as well as Toll/Interleukin-1 Receptor (TIR)-domain proteins, have central roles in innate immunity and regulated cell death in humans. In this study 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 ADP-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.
Competing Interest Statement
The authors have declared no competing interest.
