Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes.
Supplementary Exp. Proc. Henautl ...
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Riggs, Jeffrey M
Brinkmann, Melanie M
Coyle, Anthony J
Green, Douglas R
Sanjuan, Miguel A
MetadataShow full item record
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.
CitationNoncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes. 2012, 37 (6):986-97 Immunity
AffiliationRespiratory, Inflammation and Autoimmunity Research Department, MedImmune, Gaithersburg, MD 20878, USA.
The following license files are associated with this item:
- The interaction between IKKα and LC3 promotes type I interferon production through the TLR9-containing LAPosome.
- Authors: Hayashi K, Taura M, Iwasaki A
- Issue date: 2018 May 1
- Self-reactive IgE exacerbates interferon responses associated with autoimmunity.
- Authors: Henault J, Riggs JM, Karnell JL, Liarski VM, Li J, Shirinian L, Xu L, Casey KA, Smith MA, Khatry DB, Izhak L, Clarke L, Herbst R, Ettinger R, Petri M, Clark MR, Mustelin T, Kolbeck R, Sanjuan MA
- Issue date: 2016 Feb
- NLRX1 Facilitates <i>Histoplasma capsulatum</i>-Induced LC3-Associated Phagocytosis for Cytokine Production in Macrophages.
- Authors: Huang JH, Liu CY, Wu SY, Chen WY, Chang TH, Kan HW, Hsieh ST, Ting JP, Wu-Hsieh BA
- Issue date: 2018
- Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns.
- Authors: Hsiao HB, Chou AH, Lin SI, Chen IH, Lien SP, Liu CC, Chong P, Liu SJ
- Issue date: 2014 Oct
- B cell autophagy mediates TLR7-dependent autoimmunity and inflammation.
- Authors: Weindel CG, Richey LJ, Bolland S, Mehta AJ, Kearney JF, Huber BT
- Issue date: 2015