Involvement of Toll-like Receptor 3 in the Immune Response of Lung Epithelial Cells to Double-stranded RNA and Influenza A Virus*
By L. Guillot, R. Le Goffic, S. Bloch, N. Escriou, Shizuo Akira, M. Chignard, M. Si-Tahar. Journal of Biological Chemistry, 2005
730 citations recorded by the source corpus.
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-α and interleukin (IL)-1β, 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-κB 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-β and the up-regulation of the major adhesion molecule ICAM-1.
Subfields: Epidemiology, Immunology
View Paper: https://www.semanticscholar.org/paper/ec81c4e51d13ecaa9213f57905144f3405253f5b
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In Immunology
Citations in the corpus
- The Airway Epithelium: Soldier in the Fight against Respiratory Viruses (2011, background): “TLR3 responds to the presence of many respiratory viruses, including rhinoviruses (107, 137), RSV (89), and influenza viruses (90).”
- Insights into the Interaction between Influenza Virus and Pneumococcus (2006, neutral): “TLR7 and TLR8 signal through pathways similar to those stimulated by TLR2, requiring MyD88 and leading to NF- B activation, while TLR3 utilizes the same MyD88-independent pathway as TLR4, leading to IRF3 and STAT1 activation (13).”