Nature, 2009-11, Vol.462 (7269), p.99-103
2009
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses
- Ist Teil von
- Nature, 2009-11, Vol.462 (7269), p.99-103
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2009
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The activation of innate immune responses by nucleic acids is crucial to protective and pathological immunities and is mediated by the transmembrane Toll-like receptors (TLRs) and cytosolic receptors. However, it remains unknown whether a mechanism exists that integrates these nucleic-acid-sensing systems. Here we show that high-mobility group box (HMGB) proteins 1, 2 and 3 function as universal sentinels for nucleic acids. HMGBs bind to all immunogenic nucleic acids examined with a correlation between affinity and immunogenic potential. Hmgb1-/- and Hmgb2-/- mouse cells are defective in type-I interferon and inflammatory cytokine induction by DNA or RNA targeted to activate the cytosolic nucleic-acid-sensing receptors; cells in which the expression of all three HMGBs is suppressed show a more profound defect, accompanied by impaired activation of the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)- B. The absence of HMGBs also severely impairs the activation of TLR3, TLR7 and TLR9 by their cognate nucleic acids. Our results therefore indicate a hierarchy in the nucleic-acid-mediated activation of immune responses, wherein the selective activation of nucleic-acid-sensing receptors is contingent on the more promiscuous sensing of nucleic acids by HMGBs. These findings may have implications for understanding the evolution of the innate immune system and for the treatment of immunological disorders.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/nature08512Titel-ID: cdi_proquest_miscellaneous_734125314
- Format
- –
- Schlagworte
- Acids, Animals, Biological and medical sciences, Cell Line, Cells, Cytokines, Cytosol - immunology, DNA - immunology, DNA binding proteins, Fundamental and applied biological sciences. Psychology, Fundamental immunology, General aspects, Genetic aspects, Health aspects, HMGB Proteins - deficiency, HMGB Proteins - genetics, HMGB Proteins - immunology, HMGB Proteins - metabolism, HMGB1 Protein - deficiency, HMGB1 Protein - genetics, HMGB1 Protein - immunology, HMGB1 Protein - metabolism, HMGB2 Protein - deficiency, HMGB2 Protein - genetics, HMGB2 Protein - immunology, HMGB2 Protein - metabolism, Humanities and Social Sciences, Immune response, Immune system, Immunity, Innate - immunology, Interferon Regulatory Factor-3 - metabolism, letter, Mass spectrometry, Mice, Mice, Inbred C57BL, Models, Immunological, multidisciplinary, NF-kappa B - metabolism, Nucleic acids, Nucleic Acids - immunology, Nucleotides - chemistry, Nucleotides - immunology, Nucleotides - metabolism, Physiological aspects, Proteins, RNA - immunology, Science, Science (multidisciplinary), Signal Transduction, Toll-Like Receptors - immunology, Virus Diseases - immunology, Virus Diseases - virology