Extracellular NAD(P) links hypersensitive response to localized acquired resistance

Abstract Effector-triggered immunity (ETI) generates cell non-autonomous signals that activate localized acquired resistance (LAR) in neighboring cells and systemic acquired resistance (SAR) in distant tissues. While SAR signaling has been extensively characterized, the molecular basis of LAR remains poorly understood. Here, we identify extracellular nicotinamide adenine dinucleotide (eNAD(P)) as a key damage-associated molecular pattern (DAMP) that mediates LAR. Using genetic, physiological, and cell death assays, we show that eNAD(P) and its receptor complex restrict hypersensitive response (HR)-associated cell death, promote cell survival, and are required for avirulent pathogen-induced LAR. In contrast, LAR is independent of the major SAR mobile signals N-hydroxypipecolic acid and azelaic acid, as well as certain other characterized DAMP pathways. Notably, ETI-mediated resistance remains largely intact in eNAD(P) pathway mutants, indicating that ETI directly restricts pathogens while simultaneously generating eNAD(P) signals to activate LAR. Our findings establish LAR as a mechanistically distinct immune layer and link HR-associated damage to eNAD(P)-dependent local immune reinforcement. Competing Interest Statement The authors have declared no competing interest.