Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21
| Autor: | Jerry C. H. Tam, Leo C. James, William A. McEwan, Donna L. Mallery, Susanna R. Bidgood, Ruth E. Watkinson |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Protein Conformation
Immunology Intracellular Space Fc receptor Antigen-Antibody Complex Receptors Fc Cross Reactions Antibodies Viral Adenoviridae Cell Line Mice 03 medical and health sciences 0302 clinical medicine Antibody receptor Animals Humans Immunology and Allergy Protein Interaction Domains and Motifs 030304 developmental biology 0303 health sciences Innate immune system Bacteria biology RIG-I Intracellular parasite NF-kappa B Molecular biology 3. Good health Molecular Docking Simulation Transcription Factor AP-1 Ribonucleoproteins Receptors Pattern Recognition Interferon Regulatory Factors Viruses biology.protein Cytokines Inflammation Mediators Antibody Signal transduction Intracellular Protein Binding Signal Transduction 030215 immunology |
| Zdroj: | Nature Immunology. 14:327-336 |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/ni.2548 |
| Popis: | During pathogen infection, antibodies can be carried into the infected cell, where they are detected by the ubiquitously expressed cytosolic antibody receptor TRIM21. Here we found that recognition of intracellular antibodies by TRIM21 activated immune signaling. TRIM21 catalyzed the formation of Lys63 (K63)-linked ubiquitin chains and stimulated the transcription factor pathways of NF-κB, AP-1, IRF3, IRF5 and IRF7. Activation resulted in the production of proinflammatory cytokines, modulation of natural killer stress ligands and induction of an antiviral state. Intracellular antibody signaling was abrogated by genetic deletion of TRIM21 and was restored by ectopic expression of TRIM21. The sensing of antibodies by TRIM21 was stimulated after infection by DNA or RNA nonenveloped viruses or intracellular bacteria. Thus, the antibody-TRIM21 detection system provides potent, comprehensive activation of the innate immune system independently of known pattern-recognition receptors. |
| Databáze: | OpenAIRE |
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