Autophagy in inflammation, infection, and immunometabolism

• Published in: Immunity (Cambridge, Mass.) Vol. 54; no. 3; pp. 437 - 453
• Main Author: Deretic, Vojo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.03.2021; Elsevier Limited
• Subjects: Animals; Autoimmune diseases; Autoimmunity; Autophagy; Autophagy - immunology; Bacteria; Humans; Immune system; Immune System - metabolism; Immunity; Immunity, Innate; Infections; Infections - immunology; Inflammasomes; Inflammation; Inflammation - immunology; Innate immunity; Interferon; Kinases; Liver diseases; Lysosomes; Lysosomes - metabolism; Membranes; Metabolic disorders; Metabolism; Mitochondria; Neurodegeneration; Organelles; Pathogens; Phagocytosis; Proteins; Quality control; Salmonella; Signal Transduction
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2021.01.018

Autophagy is a quality-control, metabolic, and innate immunity process. Normative autophagy affects many cell types, including hematopoietic as well as non-hematopoietic, and promotes health in model organisms and humans. When autophagy is perturbed, this has repercussions on diseases with inflammatory components, including infections, autoimmunity and cancer, metabolic disorders, neurodegeneration, and cardiovascular and liver diseases. As a cytoplasmic degradative pathway, autophagy protects from exogenous hazards, including infection, and from endogenous sources of inflammation, including molecular aggregates and damaged organelles. The focus of this review is on the role of autophagy in inflammation, including type I interferon responses and inflammasome outputs, from molecules to immune cells. A special emphasis is given to the intersections of autophagy with innate immunity, immunometabolism, and functions of organelles such as mitochondria and lysosomes that act as innate immunity and immunometabolic signaling platforms. Our understanding of the immune roles of autophagy and autophagy-related processes is evolving. Deretic reviews how canonical and noncanonical autophagy protect against exogenous and endogenous sources of inflammation affecting a wide spectrum of diseases, through functions modulating type I IFN and inflammasome responses, antimicrobial defenses, immunometabolism, and immune cell subsets.