tetano
Editor, Senior Moderator
J Virol. 2013 Jan 9. [Epub ahead of print]
TLR expression and induction of type I and type III interferons in primary airway epithelial cells.
Ioannidis I, Ye F, McNally B, Willette M, Fla?o E.
Source
Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
Abstract
Interferons (IFNs) are a critical component of the first line of antiviral defense. The activation of Toll-like receptors (TLRs) expressed by dendritic cells triggers different signaling cascades that result in the production of large amounts of IFNs. However, the functional consequences of TLR activation and differential IFN production in specific cell populations other than antigen presenting cells are not fully elucidated yet. In this study, we investigated TLR expression and polarization in airway epithelial cells (AECs), and the consequences of TLR agonist stimulation for the production of type I (IFNα/β) and type III (IFNλ) IFNs. Our results show that the pattern of expression and polarization of all TLRs in primary AEC cultures mirrors that of the human airways ex-vivo, and that is receptor-specific. The anti-viral TLRs (TLR3, TLR7 and TLR9) are mostly expressed on the apical cell surface of epithelial cells in the human trachea and in primary polarized AECs. Type III IFN is the predominant IFN produced by the airway epithelium, and TLR3 is the only TLR that mediates IFN production by AECs, while all TLR agonists tested are capable of inducing AEC activation and IL-8 production. In response to influenza virus infection, AECs can produce IFNλ in an IFNAR- and STAT1-independent manner. Our results emphasize the importance of using primary well-differentiated AECs to study TLR and anti-viral responses, and provide further insight in the regulation of IFN production during the anti-viral response of the lung epithelium.
PMID:
23302870
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23302870
TLR expression and induction of type I and type III interferons in primary airway epithelial cells.
Ioannidis I, Ye F, McNally B, Willette M, Fla?o E.
Source
Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
Abstract
Interferons (IFNs) are a critical component of the first line of antiviral defense. The activation of Toll-like receptors (TLRs) expressed by dendritic cells triggers different signaling cascades that result in the production of large amounts of IFNs. However, the functional consequences of TLR activation and differential IFN production in specific cell populations other than antigen presenting cells are not fully elucidated yet. In this study, we investigated TLR expression and polarization in airway epithelial cells (AECs), and the consequences of TLR agonist stimulation for the production of type I (IFNα/β) and type III (IFNλ) IFNs. Our results show that the pattern of expression and polarization of all TLRs in primary AEC cultures mirrors that of the human airways ex-vivo, and that is receptor-specific. The anti-viral TLRs (TLR3, TLR7 and TLR9) are mostly expressed on the apical cell surface of epithelial cells in the human trachea and in primary polarized AECs. Type III IFN is the predominant IFN produced by the airway epithelium, and TLR3 is the only TLR that mediates IFN production by AECs, while all TLR agonists tested are capable of inducing AEC activation and IL-8 production. In response to influenza virus infection, AECs can produce IFNλ in an IFNAR- and STAT1-independent manner. Our results emphasize the importance of using primary well-differentiated AECs to study TLR and anti-viral responses, and provide further insight in the regulation of IFN production during the anti-viral response of the lung epithelium.
PMID:
23302870
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23302870