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PMID: 18772134 Published · ppublish English Journal Article

MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages.

The Journal of biological chemistry ·Vol. 283 ·No. 48 ·2008-11-28 ·Pages 33175-82

Shi CS, Kehrl JH

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.

MeSH Terms
Adaptor Proteins, Vesicular Transport/immunology,metabolism Animals Apoptosis Regulatory Proteins Autophagy/physiology Beclin-1 Cell Line Gene Expression Regulation/physiology Immunity, Innate/physiology Macrophages/immunology,metabolism,ultrastructure Mice Myeloid Differentiation Factor 88/immunology,metabolism Protein Binding/physiology Proteins/immunology,metabolism Proto-Oncogene Proteins/immunology,metabolism Proto-Oncogene Proteins c-bcl-2 Signal Transduction/physiology Toll-Like Receptor 4/immunology,metabolism
Chemicals
Adaptor Proteins, Vesicular Transport Apoptosis Regulatory Proteins Beclin-1 Becn1 protein, mouse Myd88 protein, mouse Myeloid Differentiation Factor 88 Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 TICAM-1 protein, mouse Tlr4 protein, mouse Toll-Like Receptor 4 Bcl2 protein, mouse
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Shi Chong-Shan
B Cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. cshi@niaid.nih.gov
Kehrl John H
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M804478200
Email
cshi@niaid.nih.gov
Published
2008-11-28
Epub
2008-00-04
Pages
33175-82
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2586260
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M804478200 PMC Full Text View journal details
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