Respiratory syncytial virus-induced activation of nuclear factor-κB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways

Helene A. Haeberle, Ryuta Takizawa, Antonella Casola, Allan R. Brasier, Hans Juergen Dieterich, Nico Van Rooijen, Zoran Gatalica, Roberto Garofalo

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196 Scopus citations

Abstract

The transcription factor nuclear factor (NF)-κB controls the expression of numerous respiratory syncytial virus (RSV)-inducible inflammatory and immunomodulatory genes. Using a BALB/c mouse model, the present article shows that RSV potently and specifically activates NF-κB in vivo, a process that involves nuclear translocation of the subunits RelA, p50, and c-Rel in the lung. By depletion of alveolar macrophages (AMs) in BALB/c mice and use of C3H/HeJ mice lacking a functional Toll-like receptor (TLR)-4 signaling pathway, we demonstrate the existence of distinct but sequentially integrated RSV-inducible early NF-κB responses in the lung. The first response occurs early after RSV inoculation, is AM and TLR4 dependent, and is viral replication independent, whereas the second response involves epithelial cells and/or inflammatory cells, is TLR4 independent, and requires viral replication. NF-κB may be considered a central activator of not only inflammatory but also innate immune responses to RSV.

Original languageEnglish
Pages (from-to)1199-1206
Number of pages8
JournalJournal of Infectious Diseases
Volume186
Issue number9
DOIs
StatePublished - Nov 1 2002

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ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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