Role of Metabolic Reprogramming in Pulmonary Innate Immunity and Its Impact on Lung Diseases.

Lung innate immunity is the first line of defence against inhaled allergens, pathogens and environmental pollutants. Cellular metabolism plays a key role in innate immunity. Catabolic pathways, including glycolysis and fatty acid oxidation (FAO), are interconnected with biosynthetic and redox pathways. Innate immune cell activation and differentiation trigger extensive metabolic changes that are required to support their function. Pro-inflammatory polarisation of macrophages and activation of dendritic cells, mast cells and neutrophils are associated with increased glycolysis and a shift towards the pentose phosphate pathway and fatty acid synthesis. These changes provide the macromolecules required for proliferation and inflammatory mediator production and reactive oxygen species for anti-microbial effects. Conversely, anti-inflammatory macrophages use primarily FAO and oxidative phosphorylation to ensure efficient energy production and redox balance required for prolonged survival. Deregulation of metabolic reprogramming in lung diseases, such as asthma and chronic obstructive pulmonary disease, may contribute to impaired innate immune cell function. Understanding how innate immune cell metabolism is altered in lung disease may lead to identification of new therapeutic targets. This is important as drugs targeting a number of metabolic pathways are already in clinical development for the treatment of other diseases such as cancer.