AUTHOR=Choudhuri Subhadip , Chowdhury Imran Hussain , Garg Nisha Jain 

TITLE=Mitochondrial Regulation of Macrophage Response Against Pathogens

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.622602

DOI=10.3389/fimmu.2020.622602

ISSN=1664-3224

ABSTRACT=<p>Innate immune cells play the first line of defense against pathogens. Phagocytosis or invasion by pathogens can affect mitochondrial metabolism in macrophages by diverse mechanisms and shape the macrophage response (proinflammatory <italic>vs</italic>. immunomodulatory) against pathogens. Besides β-nicotinamide adenine dinucleotide 2'-phosphate, reduced (NADPH) oxidase, mitochondrial electron transport chain complexes release superoxide for direct killing of the pathogen. Mitochondria that are injured are removed by mitophagy, and this process can be critical for regulating macrophage activation. For example, impaired mitophagy can result in cytosolic leakage of mitochondrial DNA (mtDNA) that can lead to activation of cGAS–STING signaling pathway of macrophage proinflammatory response. In this review, we will discuss how metabolism, mtDNA, mitophagy, and cGAS–STING pathway shape the macrophage response to infectious agents.</p>