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Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection

The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ∼35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in pat...

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Autores principales: Didierlaurent, Arnaud, Goulding, John, Patel, Seema, Snelgrove, Robert, Low, Lionel, Bebien, Magali, Lawrence, Toby, van Rijt, Leonie S., Lambrecht, Bart N., Sirard, Jean-Claude, Hussell, Tracy
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271005/
https://www.ncbi.nlm.nih.gov/pubmed/18227219
http://dx.doi.org/10.1084/jem.20070891
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author Didierlaurent, Arnaud
Goulding, John
Patel, Seema
Snelgrove, Robert
Low, Lionel
Bebien, Magali
Lawrence, Toby
van Rijt, Leonie S.
Lambrecht, Bart N.
Sirard, Jean-Claude
Hussell, Tracy
author_facet Didierlaurent, Arnaud
Goulding, John
Patel, Seema
Snelgrove, Robert
Low, Lionel
Bebien, Magali
Lawrence, Toby
van Rijt, Leonie S.
Lambrecht, Bart N.
Sirard, Jean-Claude
Hussell, Tracy
author_sort Didierlaurent, Arnaud
collection PubMed
description The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ∼35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in patients infected with influenza virus. The ability to evolve more efficient immunity on each successive encounter with antigen is the hallmark of the adaptive immune response. However, in the absence of cross-reactive T and B cell epitopes, one lung infection can modify immunity and pathology to the next for extended periods of time. We now report for the first time that this phenomenon is mediated by a sustained desensitization of lung sentinel cells to Toll-like receptor (TLR) ligands; this is an effect that lasts for several months after resolution of influenza or respiratory syncytial virus infection and is associated with reduced chemokine production and NF-κB activation in alveolar macrophages. Although such desensitization may be beneficial in alleviating overall immunopathology, the reduced neutrophil recruitment correlates with heightened bacterial load during secondary respiratory infection. Our data therefore suggests that post-viral desensitization to TLR signals may be one possible contributor to the common secondary bacterial pneumonia associated with pandemic and seasonal influenza infection.
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spelling pubmed-22710052008-08-18 Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection Didierlaurent, Arnaud Goulding, John Patel, Seema Snelgrove, Robert Low, Lionel Bebien, Magali Lawrence, Toby van Rijt, Leonie S. Lambrecht, Bart N. Sirard, Jean-Claude Hussell, Tracy J Exp Med Brief Definitive Reports The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ∼35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in patients infected with influenza virus. The ability to evolve more efficient immunity on each successive encounter with antigen is the hallmark of the adaptive immune response. However, in the absence of cross-reactive T and B cell epitopes, one lung infection can modify immunity and pathology to the next for extended periods of time. We now report for the first time that this phenomenon is mediated by a sustained desensitization of lung sentinel cells to Toll-like receptor (TLR) ligands; this is an effect that lasts for several months after resolution of influenza or respiratory syncytial virus infection and is associated with reduced chemokine production and NF-κB activation in alveolar macrophages. Although such desensitization may be beneficial in alleviating overall immunopathology, the reduced neutrophil recruitment correlates with heightened bacterial load during secondary respiratory infection. Our data therefore suggests that post-viral desensitization to TLR signals may be one possible contributor to the common secondary bacterial pneumonia associated with pandemic and seasonal influenza infection. The Rockefeller University Press 2008-02-18 /pmc/articles/PMC2271005/ /pubmed/18227219 http://dx.doi.org/10.1084/jem.20070891 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Reports
Didierlaurent, Arnaud
Goulding, John
Patel, Seema
Snelgrove, Robert
Low, Lionel
Bebien, Magali
Lawrence, Toby
van Rijt, Leonie S.
Lambrecht, Bart N.
Sirard, Jean-Claude
Hussell, Tracy
Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection
title Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection
title_full Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection
title_fullStr Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection
title_full_unstemmed Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection
title_short Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection
title_sort sustained desensitization to bacterial toll-like receptor ligands after resolutionof respiratory influenza infection
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271005/
https://www.ncbi.nlm.nih.gov/pubmed/18227219
http://dx.doi.org/10.1084/jem.20070891
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