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

Arnaud Didierlaurent, John Goulding, Seema Patel, Robert Snelgrove, Lionel Low, Magali Bebien, Toby Lawrence, Leonie S. Van Rijt, Bart N. Lambrecht, Jean Claude Sirard, Tracy Hussell

    Research output: Contribution to journalArticlepeer-review

    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-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. JEM © The Rockefeller University Press.
    Original languageEnglish
    Pages (from-to)323-329
    Number of pages6
    JournalJournal of Experimental Medicine
    Volume205
    Issue number2
    DOIs
    Publication statusPublished - 18 Feb 2008

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