Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme in cellular metabolism with a long-established role in energy production, biosynthesis, and oxidative stress responses. Recent research demonstrates that NAD hydrolysis is a key step in immune signaling, beyond its primary metabolic functions. Here, we review how NAD and NAD-derived small molecules influence defense-related processes including reactive oxygen species production, calcium dynamics, and immune activation. We introduce diverse NAD-modifying enzymes in plants and discuss how they regulate immunity, with a special emphasis on Toll/interleukin 1 receptor (TIR) domain proteins, which hydrolyze NAD+ to produce immune-activating molecules. We also discuss how pathogens use NAD-modifying enzymes as virulence factors to manipulate host defenses, highlighting NAD metabolism as a newly emerged, critical battleground in the plant-pathogen arms race. Recent developments in this aspect of pathogenesis offer new opportunities to enhance disease resistance.
Keywords: TIR domain; effector-triggered immunity; microbial pathogenesis; pathogen effectors; plant immune signaling; small molecule signals.