Autophagy in Pulmonary Innate Immunity

Abstract

Autophagy is a major intracellular digestion system that delivers cytoplasmic components for degradation and recycling. In this capacity, autophagy plays an important role in maintaining cellular homeostasis by mediating the degradation of cellular macromolecules and dysfunctional organelles and regeneration of nutrients for cell growth. Autophagy is important in innate immunity, as it is responsible for the clearance of various pathogens. Deficiency of intracellular autophagy can result in exaggerated activation of the inflammasome. The latter is an innate immune complex that senses diverse pathogen-associated or danger-associated molecular patterns and activates the expression of inflammatory cytokines. In autophagy-deficient cells, accumulation of damaged organelles, misfolded proteins, and reactive oxygen species contribute to inflammasome activation. The lung is continuously exposed to pathogens from the environment, rendering it vulnerable to infection. The lung innate immune cells act as a crucial initial barrier against the continuous threat from pathogens. In this review, we will summarize recent findings on the regulation of autophagy and its inter­action with innate immunity, focusing on the lung.

Competitive Cell Death Interactions in Pulmonary Infection: Host Modulation Versus Pathogen Manipulation

“…Based on guidelines published by the Nomenclature Committee on Cell Death, autophagy-dependent cell death is a type of RCD that relies on components of the autophagic machinery and takes place when the induction of autophagy coincides with the induction of apoptosis (24). Autophagic responses can play a key role in host defense to bacterial infections of the lung by reducing pathogen burden, but some pulmonary pathogens have evolved adaptions to benefit from such autophagic host responses or impede its execution (38,40).…”

Broad and Complex Roles of NBR1-Mediated Selective Autophagy in Plant Stress Responses

“…Autophagy is critical player in animal innate immunity for its role in protecting cells from diverse intracellular pathogens including viruses [80][81][82][83]. As an endolysosomal delivery system, autophagy can promote antiviral response through the transfer of viruses from the cytoplasm to the lysosome for degradation or the transfer of viral components to specific subcellular compartments for the activation of innate or adaptive antiviral immunity [80][81][82][83]. Likewise, autophagy plays an important role in plant antiviral defense.…”

Pseudomonas aeruginosa survives in epithelia by ExoS‐mediated inhibition of autophagy and mTOR

“…Autophagy is characterized by the formation of double‐membrane organelles called autophagosomes, which engulf cytoplasmic components and induce their degradation after fusion with lysosomes. Autophagy is a key process in innate immunity and pathogen clearance, and pathogens have evolved ways to evade autophagy (Levine & Deretic, 2007; Rao & Eissa, 2020). During lung infection by P. aeruginosa , autophagy plays an important role in mast cells and alveolar macrophages in the clearance of the bacteria (Yuan et al , 2012).…”