Nicotinamide adenine dinucleotide (NAD+) is a vital molecule found in all living cells. NAD+ intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD+ metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD+ metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD+ homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD+ or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD+ metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases.JG was supported by PD/BD/106053/2015. BV was supported by IRD (Institut de Recherche pour le Développement) institutional funding. JE was supported by a European Community’s Seventh Framework Program under grant agreement No. 602773 (Project KINDRED), an ANR grant (LEISH-APO, France) and a Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE also thanks the Canada Research Chair program for his support. RS thank FCT—Foundation for Science and Technology—for their Investigator FCT Grant (IF/00021/2014)info:eu-repo/semantics/publishedVersio
