Host NAD+ metabolism and infections: therapeutic implications

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) is both a crucial coenzyme and a cosubstrate for various metabolic reactions in all living cells. Maintenance of NAD⁺ levels is essential for cell energy homeostasis, survival, proliferation and function. Mounting evidence points to NAD⁺ as one of the major modulators of immuno-metabolic circuits, thus regulating immune responses and functions. Recent studies delineate impaired host NAD⁺ metabolism during chronic infections and inflammation, suggesting NAD⁺ replenishment as an avenue to ameliorate deleterious inflammatory responses. Here, we discuss aspects of NAD⁺ biosynthesis and consumption, NAD⁺ biology during infections and how NAD⁺ metabolism can be intervened with pharmacologically to enhance the host's immunological fitness against pathogens.