Respiratory Syncytial Virus Up-regulates TLR4 and Sensitizes Airway Epithelial Cells to Endotoxin
Open accessAbstract
Airway epithelial cells are unresponsive to endotoxin (lipopolysaccharide (LPS)) exposure under normal conditions. This study demonstrates that respiratory syncytial virus (RSV) infection results in increased sensitivity to this environmental exposure. Infection with RSV results in increased expression of Toll-like receptor (TLR) 4 mRNA, protein, and increased TLR4 membrane localization. This permits significantly enhanced LPS binding to the epithelial monolayer that is blocked by disruption of the Golgi. The increased TLR4 results in an LPS-induced inflammatory response as demonstrated by increased mitogen-activated protein (MAP) kinase activity, IL-8 production, and tumor necrosis factor alpha production. RSV infection also allowed for tumor necrosis factor alpha production subsequent to TLR4 cross-linking with an immobilized antibody. These data suggest that RSV infection sensitizes airway epithelium to a subsequent environmental exposure (LPS) by altered expression and membrane localization of TLR4. The increased interaction between airway epithelial cells and LPS has the potential to profoundly alter airway inflammation.
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RSV infection results in increased TLR4 expression on airway epithelial cells that sensitizes cells to endotoxin by enhancing LPS-receptor engagement.
“Similarly, respiratory syncytial virus (RSV) infection results in increased TLR4 expression on airway epithelial cells that sensitizes cells to endotoxin by enhancing LPS-receptor engagement (103), and TLR4 variants may attenuate innate immune responses by disrupting RSV triggering of TLR4 surface expression (142).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [103]
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- Authors
- Monick, M. M., Yarovinsky, T. O., Powers, L. S., Butler, N. S., Carter, A. B., Gudmundsson, G., & Hunninghake, G. W.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Monick, Martha M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 278
- Issue
- 52
- Pages
- 53035-53044
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2025983848
- Cited by
- 276
- References
- 48
- Citations by year
- 2025: 5 · 2024: 8 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 13 · 2013: 4 · 2012: 19
- FWCI
- 8.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health (5p50hl060316-05, 5p01es009607-05, RR00059)
- National Heart, Lung, and Blood Institute (HL 60316, HL073967-01, R01HL073967, HL-03860)
- National Institute of Environmental Health Sciences (ES09607)
- National Center for Research Resources (RR 00059, M01RR000059)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- respiratory syncytial virus, TLR4, airway epithelial cells, lipopolysaccharide, endotoxin sensitivity, Golgi apparatus, MAPK signaling, interleukin-8, TNF-α, airway inflammation, viral infection
- MeSH terms
- Cell Membrane, Cell Separation, Cells, Cultured, Cross-Linking Reagents, Dose-Response Relationship, Drug, Endotoxins, Epithelial Cells, Epithelium, Flow Cytometry, Golgi Apparatus, HeLa Cells, Humans, Inflammation, Lipopolysaccharides, Lung, Membrane Glycoproteins, Microscopy, Fluorescence, Models, Biological, Monocytes, Receptors, Cell Surface, Respiratory Syncytial Viruses, RNA, Messenger, Time Factors, Tumor Necrosis Factor-alpha, Blotting, Western, Up-Regulation, Interleukin-8, Macrophages, Alveolar, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, MAP Kinase Signaling System, Cell Line, Tumor, Toll-Like Receptors, Toll-Like Receptor 4
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