1. Respiratory Syncytial Virus--Induced Activation of Nuclear Factor--k B in the Lung Involves Alveolar Macrophages and Toll-Like Receptor 4--Dependent Pathways.
- Author
-
Haeberle, Helene A., Takizawa, Ryuta, Casola, Antonella, Brasier, Allan R., Dieterich, Hans-Juergen, van Rooijen, Nico, Gatalica, Zoran, and Garofalo, Roberto P.
- Subjects
- *
RESPIRATORY syncytial virus , *NF-kappa B , *MACROPHAGES , *IMMUNE response - 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-&kappaB 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. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF