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Review
. 2015 May;265(1):194-204.
doi: 10.1111/imr.12288.

The cooperation between the autophagy machinery and the inflammasome to implement an appropriate innate immune response: do they regulate each other?

Dalia H A Abdelaziz  1 , Hany Khalil, Estelle Cormet-Boyaka, Amal O Amer
Affiliations
Review

The cooperation between the autophagy machinery and the inflammasome to implement an appropriate innate immune response: do they regulate each other?

Dalia H A Abdelaziz et al. Immunol Rev. 2015 May.

Abstract

Autophagy is originally described as the main catabolic pathway responsible for maintaining intracellular nutritional homeostasis that involves the formation of a unique vacuole, the autophagosome, and the interaction with the endosome-lysosome pathways. This conserved machinery plays a key role in immune-protection against different invaders, including pathogenic bacteria, intracellular parasites, and some viruses like herpes simplex and hepatitis C virus. Importantly, autophagy is linked to a number of human diseases and disorders including neurodegenerative disease, Crohn's disease, type II diabetes, tumorigenesis, cardiomyopathy, and fatty liver disease. On the other hand, inflammasomes are multiprotein platforms stimulated upon several environmental conditions and microbial infection. Once assembled, the inflammasomes mediate the maturation of pro-inflammatory cytokines and promote phagosome-lysosome fusion to sustain an innate immune response. The intersections between autophagy and inflammasome have been observed in various diseases and microbial infections. This review highlights the molecular aspects involved in autophagy and inflammasome interactions during different medical conditions and microbial infections.

Keywords: Toll-like receptors/pattern recognition receptors; autophagy; bacteria; cell trafficking; monocytes/macrophages.

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Figures

Fig. 1
Fig. 1. Schematic representation of molecular interaction between autophagosomes and members of the inflammasome
NOD-like receptors (NLRs) sense bacterial or viral molecules leading to the assembly of the inflammasome complex. (A) Autophagy can uptake certain invading organisms. The inflammasome complex is composed of the NLR, the adapter molecule ASC, and caspase-1 (B). Members of the inflammasome are ubiquitinated and then targeted by autophagosomes (B). The inflammasome can be activated by reactive oxygen species (ROS) released from mitochondria that were not cleared by autophagosomes (C). NLRs bind beclin-1, and upon their recruitment to the inflammasome complex, beclin-1 is released and contributes to the formation of autophagosomes (D). Autophagosomes also target pro-IL-1β to maintain its level under control (E). The inflammasome complex cleaves pro-IL-1β leading to active IL-1β. Active IL-1β is escorted outside the cell within autophagosomes (F). IL-1β inhibits autophagosome formation via unknown mechanisms (G). Mutant protein aggregates are targeted by autophagy to clear them from the cytosol; however, if they accumulate, autophagy molecules will be sequestered reducing their availability to form autophagosomes (H). Red arrows depict pathways by which the inflammasome contributes to the modulation of autophagy.
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References

    1. Tschopp J, Schroder K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol. 2010;10:210–215. - PubMed
    1. Fantuzzi G, Dinarello CA. Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase-1) J Clin Immunol. 1999;19:1–11. - PubMed
    1. Choi AJ, Ryter SW. Autophagy in inflammatory diseases. Int J Cell Biol. 2011;2011:732798. - PMC - PubMed
    1. Harris J. Autophagy and IL-1 family cytokines. Front Immunol. 2013;4:83. - PMC - PubMed
    1. Harris J, et al. Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. J Biol Chem. 2011;286:9587–9597. - PMC - PubMed

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