An evolutionarily conserved module links TIR signaling to disease resistance

The Toll/interleukin-1 receptor (TIR) domain, a conserved immune signaling module across all kingdoms, is frequently fused to other domains to enhance host defense against microbial pathogens. TIR domains exhibit multifunctional enzymatic activities, catalyzing diverse substrates into structurally distinct nucleotide metabolites that serve as second messengers to couple TNL signaling to RNL activation. Two recent studies published in Science revealed that the EDS1–PAD4–ADR1 signaling module, which transduces TIR enzymatic activity into immune responses, is evolutionarily conserved in both monocots and dicots. Remarkably, this module is activated not only by plant TIR domains but also by bacterial TIR domains. Advancing our understanding of cross-kingdom TIR enzymatic functions and their downstream signaling mechanisms offers promising strategies for engineering durable disease resistance in crops.