Autophagy-Inflammation Interplay During Infection: Balancing Pathogen Clearance and Host Inflammation

Abstract

Inflammation is an essential immune response of the host against infections but is often over-activated, leading to a variety of disorders. Autophagy, a conserved degradation pathway, also protects cells by capturing intracellular pathogens that enter the cell and transporting them to the lysosome for clearance. Dysfunctional autophagy is often associated with uncontrolled inflammatory responses during infection. In recent years, more and more research has focused on the crosstalk between autophagy and inflammation. In this paper, we review the latest research advances in this field, hoping to gain insight into the mechanisms by which the body balances autophagy and inflammation in infections and how this mechanism can be used to fight infections better.

Keywords: autophagy; bacteria; infection; inflammasome; inflammation; microbial; virus.

FIGURE 1

Induction and regulation of autophagy during pathogen infection. Bacterial, viral, and inflammatory signals can all induce autophagy initiation. After autophagy initiation, dispersed intracellular membrane vesicles are induced to nucleate and form phagophores. The nucleation induction is regulated by mTOR, AMPK and ULK1 (Atg1 in yeast) and the Class III PI3K complexes containing Beclin1 (Atg6 in yeast), Atg14 and other proteins. The phagophore extends and wraps around the autophagic cargos (e.g., intracellular bacteria and viruses, DAMPs), expanding and closing under two ubiquitin-like Atg5-Atg12 and Atg8 (LC3 in mammals) ligation systems to form the bilayer membrane structure of autophagosomes. Finally, autophagosomes fuse with lysosomes to form the monolayer autophagolysosomes, degrading the enclosed cargos and recycling membrane structures with Atg9.

FIGURE 2

Crosstalks between autophagy and inflammation during pathogen infections. Bacterial and viral infections trigger inflammation by activating NF-κB signaling and inflammasome. Autophagy negatively regulates inflammation by degrading its stimuli, including bacteria, viruses, DAMPs, and inflammasome components. Rapamycin and overexpression of autophagy genes (such as Atg5, Atg7, Atg16L1, and ATP6V0D2) reduce inflammation by promoting autophagy, while 3-MA, inflammasome components (e.g., Ipaf, Caspase-1) and pathogen encoded proteins preserve inflammation by antagonizing autophagy.