Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes.

2.50
Hdl Handle:
http://hdl.handle.net/10033/281033
Title:
Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes.
Authors:
Henault, Jill; Martinez, Jennifer; Riggs, Jeffrey M; Tian, Jane; Mehta, Payal; Clarke, Lorraine; Sasai, Miwa; Latz, Eicke; Brinkmann, Melanie M; Iwasaki, Akiko; Coyle, Anthony J; Kolbeck, Roland; Green, Douglas R; Sanjuan, Miguel A
Abstract:
Toll-like receptor-9 (TLR9) is largely responsible for discriminating self from pathogenic DNA. However, association of host DNA with autoantibodies activates TLR9, inducing the pathogenic secretion of type I interferons (IFNs) from plasmacytoid dendritic cells (pDCs). Here, we found that in response to DNA-containing immune complexes (DNA-IC), but not to soluble ligands, IFN-α production depended upon the convergence of the phagocytic and autophagic pathways, a process called microtubule-associated protein 1A/1B-light chain 3 (LC3)-associated phagocytosis (LAP). LAP was required for TLR9 trafficking into a specialized interferon signaling compartment by a mechanism that involved autophagy-related proteins, but not the conventional autophagic preinitiation complex, or adaptor protein-3 (AP-3). Our findings unveil a new role for nonconventional autophagy in inflammation and provide one mechanism by which anti-DNA autoantibodies, such as those found in several autoimmune disorders, bypass the controls that normally restrict the apportionment of pathogenic DNA and TLR9 to the interferon signaling compartment.
Affiliation:
Respiratory, Inflammation and Autoimmunity Research Department, MedImmune, Gaithersburg, MD 20878, USA.
Citation:
Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes. 2012, 37 (6):986-97 Immunity
Journal:
Immunity
Issue Date:
14-Dec-2012
URI:
http://hdl.handle.net/10033/281033
DOI:
10.1016/j.immuni.2012.09.014
PubMed ID:
23219390
Type:
Article
Language:
en
ISSN:
1097-4180
Appears in Collections:
junior research group immunomodulation (VIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorHenault, Jillen_GB
dc.contributor.authorMartinez, Jenniferen_GB
dc.contributor.authorRiggs, Jeffrey Men_GB
dc.contributor.authorTian, Janeen_GB
dc.contributor.authorMehta, Payalen_GB
dc.contributor.authorClarke, Lorraineen_GB
dc.contributor.authorSasai, Miwaen_GB
dc.contributor.authorLatz, Eickeen_GB
dc.contributor.authorBrinkmann, Melanie Men_GB
dc.contributor.authorIwasaki, Akikoen_GB
dc.contributor.authorCoyle, Anthony Jen_GB
dc.contributor.authorKolbeck, Rolanden_GB
dc.contributor.authorGreen, Douglas Ren_GB
dc.contributor.authorSanjuan, Miguel Aen_GB
dc.date.accessioned2013-04-12T12:07:26Z-
dc.date.available2013-04-12T12:07:26Z-
dc.date.issued2012-12-14-
dc.identifier.citationNoncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes. 2012, 37 (6):986-97 Immunityen_GB
dc.identifier.issn1097-4180-
dc.identifier.pmid23219390-
dc.identifier.doi10.1016/j.immuni.2012.09.014-
dc.identifier.urihttp://hdl.handle.net/10033/281033-
dc.description.abstractToll-like receptor-9 (TLR9) is largely responsible for discriminating self from pathogenic DNA. However, association of host DNA with autoantibodies activates TLR9, inducing the pathogenic secretion of type I interferons (IFNs) from plasmacytoid dendritic cells (pDCs). Here, we found that in response to DNA-containing immune complexes (DNA-IC), but not to soluble ligands, IFN-α production depended upon the convergence of the phagocytic and autophagic pathways, a process called microtubule-associated protein 1A/1B-light chain 3 (LC3)-associated phagocytosis (LAP). LAP was required for TLR9 trafficking into a specialized interferon signaling compartment by a mechanism that involved autophagy-related proteins, but not the conventional autophagic preinitiation complex, or adaptor protein-3 (AP-3). Our findings unveil a new role for nonconventional autophagy in inflammation and provide one mechanism by which anti-DNA autoantibodies, such as those found in several autoimmune disorders, bypass the controls that normally restrict the apportionment of pathogenic DNA and TLR9 to the interferon signaling compartment.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Immunityen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAntigen-Antibody Complexen_GB
dc.subject.meshAutophagyen_GB
dc.subject.meshDNAen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunoglobulin Gen_GB
dc.subject.meshInterferon Type Ien_GB
dc.subject.meshMembrane Transport Proteinsen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Knockouten_GB
dc.subject.meshMicrotubule-Associated Proteinsen_GB
dc.subject.meshPhagocytosisen_GB
dc.subject.meshPhagosomesen_GB
dc.subject.meshProtein Transporten_GB
dc.subject.meshToll-Like Receptor 9en_GB
dc.titleNoncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes.en
dc.typeArticleen
dc.contributor.departmentRespiratory, Inflammation and Autoimmunity Research Department, MedImmune, Gaithersburg, MD 20878, USA.en_GB
dc.identifier.journalImmunityen_GB

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