Abstract
Purine-based metabolites serve as essential mediators of signaling, immunity, and host-microbe interactions across biological kingdoms. This review explores their extracellular and intracellular functions, focusing on well-characterized molecules as well as emerging players, and examines the conserved and divergent mechanisms underlying purine-mediated responses in plants and animals, with comparative insights into microbial strategies that influence or exploit these pathways. Key topics include the role of extracellular adenosine triphosphate in immune responses, the dual function of NAD+ as both a metabolic cofactor and signaling molecule, and the emerging roles of deoxynucleosides and cyclic nucleotides in stress and immunity regulation. Special emphasis is placed on Toll/interleukin-1 receptor (TIR) domain-containing proteins, which generate novel purine-derived infochemicals-bioactive signaling metabolites that regulate immune responses and cell death while modulating host-microbe interactions. By integrating insights across biological kingdoms, this review underscores the potential of purine-based signaling molecules and their natural and chemically modified functional derivatives as targets for therapeutic and agricultural innovation, bridging fundamental discoveries with practical applications. Finally, moving beyond purine-based metabolites, we offer a new perspective on immunometabolism and infochemicals as fundamental regulators of host-microbe interactions, shaping defense, modulating metabolism, facilitating symbiosis, and driving broader evolutionary dynamics.