Involvement of Toll-like Receptor 3 in the Immune Response of Lung Epithelial Cells to Double-stranded RNA and Influenza A Virus
Open accessAbstract
Influenza A is a highly contagious single-stranded RNA virus that infects both the upper and lower respiratory tracts of humans. The host innate immune Toll-like receptor (TLR) 3 was shown previously in cells of myeloid origin to recognize the viral replicative, intermediate double-stranded RNA (dsRNA). Thus, dsRNA may be critical for the outcome of the infection. Here we first compared the activation triggered by either influenza A virus or dsRNA in pulmonary epithelial cells. We established that TLR3 is constitutively expressed in human alveolar and bronchial epithelial cells, and we describe its intracellular localization. Expression of TLR3 was positively regulated by the influenza A virus and by dsRNA but not by other inflammatory mediators, including bacterial lipopolysaccharide, the cytokines tumor necrosis factor-alpha and interleukin (IL)-1beta, and the protein kinase C activator phorbol 12-myristate 13-acetate. We also demonstrated that TLR3 contributes directly to the immune response of respiratory epithelial cells to influenza A virus and dsRNA, and we propose a molecular mechanism by which these stimuli induce epithelial cell activation. This model involves mitogen-activated protein kinases, phosphatidylinositol 3-kinase/Akt signaling, and the TLR3-associated adaptor molecule TRIF but not MyD88-dependent activation of the transcription factors NF-kappaB or interferon regulatory factor/interferon-sensitive response-element pathways. Ultimately, this signal transduction elicits an epithelial response that includes the secretion of the cytokines IL-8, IL-6, RANTES (regulated on activation normal T cell expressed and secreted), and interferon-beta and the up-regulation of the major adhesion molecule ICAM-1.
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Increased pneumococcal adherence was found after prior adenovirus or rhinovirus infection of airway epithelial cells.
“and increased pneumococcal adherence was found after prior adenovirus or rhinovirus infection of airway epithelial cells (93, 302).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [93]
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- Authors
- Guillot, L., Le Goffic, R., Bloch, S., Escriou, N., Akira, S., Chignard, M., & Si-Tahar, M.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 280
- Issue
- 7
- Pages
- 5571-5580
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2057704272
- Cited by
- 689
- References
- 42
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 15 · 2023: 12 · 2022: 22 · 2021: 22 · 2020: 31 · 2019: 22 · 2018: 31 · 2017: 33 · 2016: 24 · 2015: 31 · 2014: 43 · 2013: 32 · 2012: 39
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Keywords
- TLR3, influenza A virus, double-stranded RNA, lung epithelial cells, alveolar epithelial cells, bronchial epithelial cells, innate immunity, TRIF, phosphatidylinositol 3-kinase/Akt signaling, mitogen-activated protein kinase, cytokine production, interferon-beta, ICAM-1
- MeSH terms
- Antigens, Differentiation, Epithelial Cells, Gene Expression Regulation, Humans, Interferons, Interleukin-1, Lipopolysaccharides, Lung, Membrane Glycoproteins, Influenza A virus, Poly I-C, Proto-Oncogene Proteins, Receptors, Cell Surface, Receptors, Immunologic, RNA, Double-Stranded, Tetradecanoylphorbol Acetate, Tumor Necrosis Factor-alpha, Signal Transduction, Up-Regulation, Cytokines, NF-kappa B, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Response Elements, Protein Transport, Extracellular Signal-Regulated MAP Kinases, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Toll-Like Receptors, Toll-Like Receptor 3, Myeloid Differentiation Factor 88
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