Cystic fibrosis and normal human airway epithelial cell response to influenza a viral infection.
Viral infections produce severe respiratory morbidity in children with cystic fibrosis (CF). CF cells are more susceptible to virus in part because of impaired airway epithelial activation of signal transducer and activator of transcription 1 (Stat1). As Stat1 is a fundamental regulator of antiviral defenses, we hypothesized that there may be multiple alterations in the antiviral defense of CF epithelium compared with normal (NL). To obtain a comprehensive view of mucosal host responses to influenza and characterize the difference between CF and NL responses to influenza, gene expression profiles of primary human airway epithelial cells (HAEC) were evaluated using an interferon (IFN)-stimulated genes/AU/double-stranded RNA (dsRNA) microarray or quantitative real-time polymerase chain reaction (PCR) following influenza A infection. Gene expression was significantly modified by influenza in NL (228 genes) and CF (101 genes), with a similar pattern of gene response but with overall less numbers of responsive genes in CF (p < 0.05). Moreover, CF cells had less IFN-related antiviral gene induction at 24 h but greater inflammatory cytokine gene induction at 1 h after infection. Taken together, the lesser antiviral and greater early inflammatory response likely contribute to the severe respiratory illness of CF patients with viral infections.
Xu
Weiling
W
Department of Pathobiology and Pulmonary Allergy and Critical Care Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Zheng
Shuo
S
Goggans
Tannishia M
TM
Kiser
Patti
P
Quinones-Mateu
Miguel E
ME
Janocha
Allison J
AJ
Comhair
Suzy A A
SA
Slee
Roger
R
Williams
Bryan R G
BR
Erzurum
Serpil C
SC
D002478:Cells, Cultured; D002648:Child; D003550:Cystic Fibrosis / Q000473:pathology* / Q000503:physiopathology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology* / Q000821:virology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D007251:Influenza, Human; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D020545:Respiratory Mucosa / Q000166:cytology* / Q000276:immunology / Q000821:virology; D015533:Transcriptional Activation