Work

Disruption of glucose homeostasis by bacterial infection orchestrates host innate immunity through NAD+/NADH balance

Year: 2024

Type: article

Abstract: Metabolic reprogramming is crucial for activating innate immunity in macrophages, and the accumulation of immunometabolites is essential for effective defense against infection. The NAD + /NADH (ratio of nicotinamide adenine dinucleotide and its reduced counterpart) redox couple serves as a critical node that integrates metabolic pathways and signaling events, but how this metabolite couple engages macrophage activation remains unclear. Here, we show that the NAD + /NADH ratio serves as a molecular signal that regulates proinflammatory responses and type I interferon (IFN) responses divergently. Salmonella Typhimurium infection leads to a decreased NAD + /NADH ratio by inducing the accumulation of NADH. Further investigation shows that an increased NAD + /NADH ratio correlates with attenuated proinflammatory responses and enhanced type I IFN responses. Conversely, a decreased NAD + /NADH ratio is linked to intensified proinflammatory responses and restrained type I IFN responses. These results show that the NAD + /NADH ratio is an essential cell-intrinsic factor that orchestrates innate immunity, which enhances our understanding of how metabolites fine-tune innate immunity.

Source: Cell Reports

DOI: 10.1016/j.celrep.2024.114648