Multiple immune functions of plant TIR domain proteins

Toll-interleukin-1 receptor (TIR) domain is a conserved immune module in animals, plants and bacteria. Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal TIR domain recognize pathogen effectors to form resistosomes, which activates the NADase activity of the TIR domain to generate small molecules for immune activation. Interestingly, plants also encode truncated TIR domain proteins. Here we show that TIR domain proteins form biomolecular condensates in the present of NAD⁺/ATP, thereby activating NADase activity and triggering hypersensitive response (HR). Furthermore, TIR domain proteins can hydrolyze DNA/RNA to produce 2’3’-cAMP/cGMP, thus promoting immune response. Taken together, our findings reveal multiple biochemical functions of TIR domain proteins in plant immunity.