Localization of type I interferon receptor limits interferon-induced TLR3 in epithelial cells.
Previous studies have shown that influenza infections increase Toll-like receptor 3 (TLR3) expression and that type I interferons (IFNs) may play a role in this response. This study aimed to expand on the role of type I IFNs in the influenza-induced upregulation of TLR3 and determine whether and how the localization of the IFN-alpha/beta receptor (IFNAR) in respiratory epithelial cells could modify IFN-induced responses. Using differentiated primary human airway epithelial cells this study demonstrates that soluble mediators secreted in response to influenza infection upregulate TLR3 expression in naive cells. This response was associated with an upregulation of type I IFNs and stimulation with type I, but not type II, IFNs enhanced TLR3 expression. Interestingly, although influenza infection results in IFN-beta release both toward the apical and basolateral sides of the epithelium, TLR3 expression is only enhanced in cells stimulated with IFN-beta from the basolateral side. Immunohistochemical analysis demonstrates that IFNAR expression is limited to the basolateral side of differentiated human airway epithelial cells. However, non- or poorly differentiated epithelial cells express IFNAR more toward the apical side. These data demonstrate that restricted expression of the IFNAR in the differentiated airway epithelium presents a potential mechanism of regulating type I IFN-induced TLR3 expression.
Ciencewicki
Jonathan M
JM
Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27599-7310, USA.
Brighton
Luisa E
LE
Jaspers
Ilona
I
D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism*; D012996:Solutions; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*
D012996:Solutions; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D053633:Receptor, Interferon alpha-beta; D007372:Interferons