Autophagy Shapes Inflammation

Autophagy is a basic cell biological process ongoing under physiologic circumstances in almost all cell types of the human organism and upregulated by various stress conditions including those leading to inflammation. Since autophagy affects the effector cells of innate and adaptive immunity mediating the inflammatory response, its activity in these cells influences the antimicrobial response, the development of an effective cognate immune defense, and the course of the normal sterile inflammatory reactions. The level of autophagic activity may determine whether tissue cells die by apoptosis, necrosis, or through autophagy, and, as a consequence, whether the clearance of these dying cells is a silent process or results in an inflammatory response. Loss or decreased autophagy may lead to necrotic death that can initiate an inflammatory reaction in phagocytes through their surface and cytosolic receptors. Engulfment of certain cells dying through autophagy can activate the inflammasome. The intertwining regulatory connections between inflammation and immunity extend to pathologic conditions including chronic inflammatory diseases, autoimmunity and cancer.