Document Detail


Autophagy as an innate immunity paradigm: expanding the scope and repertoire of pattern recognition receptors.
MedLine Citation:
PMID:  22118953     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 alarmins 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 virus, 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.
Authors:
Vojo Deretic
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-24
Journal Detail:
Title:  Current opinion in immunology     Volume:  -     ISSN:  1879-0372     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8900118     Medline TA:  Curr Opin Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
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