| First Author | Henault J | Year | 2012 |
| Journal | Immunity | Volume | 37 |
| Issue | 6 | Pages | 986-997 |
| PubMed ID | 23219390 | Mgi Jnum | J:191056 |
| Mgi Id | MGI:5460906 | Doi | 10.1016/j.immuni.2012.09.014 |
| Citation | Henault J, et al. (2012) Noncanonical Autophagy Is Required for Type I Interferon Secretion in Response to DNA-Immune Complexes. Immunity 37(6):986-97 |
| abstractText | 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-alpha 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. |
