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J. Exp. Med. 205 (2): 323-329

Copyright © 2008 by the Rockefeller University Press.

BRIEF DEFINITIVE REPORT

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

Arnaud Didierlaurent1, John Goulding1, Seema Patel1, Robert Snelgrove1, Lionel Low1, Magali Bebien1, Toby Lawrence1, Leonie S. van Rijt2, Bart N. Lambrecht2, Jean-Claude Sirard3, , and Tracy Hussell1

1 Kennedy Institute of Rheumatology, Imperial College London, London W6 8LH, England, UK
2 Department of Pulmonary Medicine, Erasmus Medical Center, 3015 GE Rotterdam, Netherlands
3 INSERM U801, Equipe Avenir d'Immunité Anti-Microbienne des Muqueuses, Institut Pasteur de Lille-Institut de Biologie, 59000 Lille, France

CORRESPONDENCE Tracy Hussell: t.hussell{at}imperial.ac.uk OR Arnaud Didierlaurent: a.didierlaurent{at}imperial.ac.uk

Abstract: 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-{kappa}B 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.

M. Bebien and T. Lawrence's present address is Institute of Cancer, Centre for Translational Oncology, Bart's and The London School of Medicine and Dentistry, London EC1M 6BQ, UK.

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