Respiratory syncytial virus-induced activation of nuclear factor-kappaB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways.
The transcription factor nuclear factor (NF)-kappaB 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-kappaB 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-kappaB may be considered a central activator of not only inflammatory but also innate immune responses to RSV.
Haeberle
Helene A
HA
Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas 77555, USA. helene.haeberle@uni-tuebingen.de
Takizawa
Ryuta
R
Casola
Antonella
A
Brasier
Allan R
AR
Dieterich
Hans-Juergen
HJ
Van Rooijen
Nico
N
Gatalica
Zoran
Z
Garofalo
Roberto P
RP
D000818:Animals; D029721:Drosophila Proteins; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000821:virology*; D016676:Macrophages, Alveolar / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism*; D021122:Protein Subunits; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018357:Respiratory Syncytial Virus Infections / Q000503:physiopathology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors