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Deretic, V. (2012). Autophagy as an innate immunity paradigm: Expanding the scope and repertoire of pattern recognition receptors. Current Opinion in Immunology, 24(1), 21–31. Added by: Dr. Enrique Feoli (07/05/2022, 17:55) Last edited by: Dr. Enrique Feoli (07/05/2022, 18:01) |
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| Resource type: Journal Article DOI: 10.1016/j.coi.2011.10.006 ID no. (ISBN etc.): 0952-7915 BibTeX citation key: Deretic2012 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Constitutive innate immunity Creators: Deretic Collection: Current Opinion in Immunology |
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| Abstract |
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Autophagy is rapidly developing into a new immunological paradigm. The latest links now include overlaps between autophagy and innate immune signaling via TBK-1 and IKKα/β, and the role of autophagy in inflammation directed by the inflammasome. Autophagy's innate immunity connections include responses to pathogen and damage associated molecular patterns including alarming such as HMGB1 and IL-1β, Toll-like receptors, Nod-like receptors including NLRC4, NLRP3 and NLRP4, and RIG-I-like receptors. Autophagic adaptors referred to as SLRs (sequestosome 1/p62-like receptors) are themselves a category of pattern recognition receptors. SLRs empower autophagy to eliminate intracellular microbes by direct capture and by facilitating generation and delivery of antimicrobial peptides, and also serve as inflammatory signaling platforms. SLRs contribute to autophagic control of intracellular microbes, including Mycobacterium tuberculosis, Salmonella, Listeria, Shigella, HIV-1 and Sindbis viruses, but act as double edged sword and contribute to inflammation and cell death. Autophagy roles in innate immunity continue to expand vertically and laterally, and now include antimicrobial function downstream of vitamin D3 action in tuberculosis and AIDS. Recent data expand the connections between immunity related GTPases and autophagy to include not only IRGM but also several members of the Gbp (guanlyate-binding proteins) family. The efficacy with which autophagy handles microbes, microbial products and sterile endogenous irritants governs whether the outcome will be with suppression of or with excess inflammation, the latter reflected in human diseases that have strong inflammatory components including tuberculosis and Crohn's disease.
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| Notes |
Concluding remarksAutophagy is intimately intertwined with nearly all aspects of innate immunity, attesting to the contention that immunological functions are one of autophagy's mainstream roles. In this opinion article we have focused on the interrelationship between autophagy and conventional innate immunity systems including TLRs, RLRs, NLRs, and inflammasomes. Additionally, we have ascribed a PRR function to the autophagic adaptors (SLRs), such as p62/sequestosome 1, NBR1, NDP52, and optineurin, characterized by the presence of LC3-interacting region, ability to recognize and target for autophagy the invading intracellular microbes, and propensity to connect with proinflammatory signaling. A common theme emerges whereby different PRRs, now including a new category, the SLRs, coordinate cell-autonomous capture of intracellular microbes with other aspects of innate immunity responses. We propose that, among the PRRs, what sets apart the SLRs is that they have a unique capability of executing their antimicrobial function in full without having to trigger inflammation, but can switch to a pro-inflammatory mode when needed (Fig. 4). If the autophagic clearance of microbes fails, SLRs can trigger pro-inflammatory signaling at cellular and tissue levels to recruit additional forces and limit the spread of infection. In keeping with the dual anti-inflammatory and pro-inflammatory capabilities of autophagy as an innate immunity mechanism, basal autophagy keeps inflammasomes from being spuriously activated by intracellular triggers, but induced autophagy can augment inflammasome-dependent processing and secretion of potent pro-inflammatory DAMPs/alarmins IL-1β and HMGB1. Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |