Autophagy limits activation of the inflammasomes

Abstract

Inflammasomes are multiprotein complexes that control the maturation and production of interleukin-1 family members and play crucial roles in host defense against pathogens. However, dysregulated activation of inflammasomes is associated with intense inflammation, leading to the development of inflammatory diseases. Therefore, inflammasomes must be activated at a proper strength to protect against infection and avoid tissue damage. Recent studies have highlighted the cross-talk between inflammasome activation and autophagy, the cellular machinery associated with the degradation of intracellular components and maintenance of cellular homeostasis. Notably, deficiencies in autophagy-related proteins induce the aberrant activation of inflammasomes, causing severe tissue damage. In contrast, autophagy inducers ameliorate symptoms of inflammasome-related diseases. In this review, we discuss recent advances in the involvement of autophagy in regulating inflammasomes activation and in the development of inflammatory diseases.

Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection

“…Since autophagy is initiated at early time points after infection it could be considered as a first line of NLRP3‐mediated control of T. cruzi replication, with NO secretion acting as an additional effector mechanism to clear the parasite. Actually, the interplay between autophagy and inflammasomes have been extensively studied in the context of many physiologic and pathologic conditions, including infectious diseases . However, since both autophagy and inflammasomes participate in unique host pathogens interactions, the networks built during infections are very complex and, therefore could account for the controversial data found in the literature.…”

“…At present, the mechanisms involved in the modulation of inflammasomes by autophagy are far better known. They involve the direct degradation of inflammasome components by autolysosomes as well as the indirect “removal” of inflammasome activators, such as damaged mitochondrias, limiting the release of its DNA and reactive oxygen species . On the other hand, inflammasomes, as well as other families of PRRs, have both stimulatory and inhibitory roles in the autophagy process during infections and the outcome seems to depend on the host‐pathogen interaction, since pathogens have evolved multiple strategies to subvert these pathways .…”

The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders

“…Autophagy and IFN-mediated immunity are meticulously balanced in healthy individuals. Dysfunction in this balance can lead to auto-immune disorders, such as CD (reviewed in Deretic, 2016; Plantinga et al, 2012; Takahama et al, 2018). Autophagy is a degradation process that has been tied to antiviral innate immune responses.…”

Autophagy in Inflammation: the p38α MAPK-ULK1 Axis

“…Innate immune cells respond to endogenous or exogenous irritations and injuries. The inflammatory response can be either protective or destructive depending on the context of the insults and the stage of the response [5] . Recent studies have highlighted the cross-talk between autophagy and inflammation.…”