title: MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages.
abstract: The Toll-like receptors (TLR) play an instructive role in innate and adaptive immunity by recognizing specific molecular patterns from pathogens. Autophagy removes intracellular pathogens and participates in antigen presentation. Here, we demonstrate that not only TLR4, but also other TLR family members induce autophagy in macrophages, which is inhibited by MyD88, Trif, or Beclin 1 shRNA expression. MyD88 and Trif co-immunoprecipitate with Beclin 1, a key factor in autophagosome formation. TLR signaling enhances the interaction of MyD88 and Trif with Beclin 1, and reduces the binding of Beclin 1 to Bcl-2. These findings indicate TLR signaling via its adaptor proteins reduces the binding of Beclin 1 to Bcl-2 by recruiting Beclin 1 into the TLR-signaling complex leading to autophagy.
authors.affiliation: B Cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. cshi@niaid.nih.gov
authors.forename: Chong-Shan
authors.initials: CS
authors.lastname: Shi
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D053594:Myeloid Differentiation Factor 88; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051197:Toll-Like Receptor 4; C115010:Becn1 protein, mouse; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse; C052617:Bcl2 protein, mouse
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