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

Research output: Contribution to journalArticle

  • External authors:
  • Arnaud Didierlaurent
  • John Goulding
  • Seema Patel
  • Robert Snelgrove
  • Lionel Low
  • Magali Bebien
  • Toby Lawrence
  • Leonie S. Van Rijt
  • Bart N. Lambrecht
  • Jean Claude Sirard

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)323-329
Number of pages6
JournalJournal of Experimental Medicine
Volume205
Issue number2
DOIs
Publication statusPublished - 18 Feb 2008