Mechanisms of Plant Immune Receptor Function: What are Toll/interleukin receptor-1 Domains Doing in Plants?

Plants employ a diverse intracellular system of NLR (nucleotide binding–leucine-rich repeat) innate immune receptors to detect pathogens of all types. These receptors represent valuable agronomic traits that plant breeders rely on to maximize yield in the face of devastating pathogens. Plant NLR immune receptors activate cell death and confer resistance to pathogens. Despite their importance, the mechanistic underpinnings of NLR-based disease resistance have been obscure. Intriguingly, we’ve found that plant TIR (Toll/interleukin-1 receptor) domains are enzymes capable of degrading NAD+. Cell death induction and the NADase activity of plant ‘TIR-only’ proteins and TIR domains derived from TIR-NBS-LRR (TNL) immune receptors require known self-association interfaces and a putative catalytic glutamic acid conserved in both bacterial TIR NADases and the mammalian SARM1 TIR NADase. We’ve identified a variant form of cADPR as an in vitro TIR-dependent NAD+ breakdown product and an in planta biomarker of TIR enzymatic activity. TIR enzymatic activity is induced by pathogen recognition, and functions upstream of EDS1 and NRG1, two proteins required for TIR immune function. Thus, plant TIR-NLR receptors require a conserved enzymatic function to transduce recognition of pathogens into a cell death response.