Normal and Cystic Fibrosis Human Bronchial Epithelial Cells Infected with Pseudomonas aeruginosa Exhibit Distinct Gene Activation Patterns.
OBJECTIVE
In cystic fibrosis (CF), Pseudomonas aeruginosa is not eradicated from the lower respiratory tract and is associated with epithelial inflammation that eventually causes tissue damage. To identify the molecular determinants of an effective response to P. aeruginosa infection, we performed a transcriptomic analysis of primary human bronchial epithelial cells from healthy donors (CTRL) 2, 4, and 6 h after induced P. aeruginosa infection. Compared to noninfected cells, infected cells showed changes in gene activity, which were most marked 6 h postinfection and usually consisted in upregulation.


RESULTS
By comparing for each time point of infection, the transcriptomic response of epithelial cells from CF patients and healthy donors, we identified 851, 638, 667, and 980 differentially expressed genes 0, 2, 4, and 6 h postinfection, respectively. Gene selection followed by bioinformatic analysis showed that most of the differentially expressed genes, either up- or downregulated, were in the protein-binding and catalytic gene-ontology categories. Finally, we established that the protein products of the genes exhibiting the greatest differential upregulation (CSF2, CCL2, TNF, CSF3, MMP1, and MMP10) between CF patients and CTRL were produced in higher amounts by infected cells from CF patients versus CTRL.


CONCLUSIONS
The differentially expressed genes in CF patients may constitute a signature for a detrimental inflammatory response and for an inefficient P. aeruginosa host-cell response.
INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France.
Viviane
V
Balloy
Institut Pasteur, Plate-forme Transcriptome Epigenome, Centre Innovation et Recherche Technologiques, Paris, France.
Hugo
H
Varet
Institut Pasteur, Plate-forme Transcriptome Epigenome, Centre Innovation et Recherche Technologiques, Paris, France.
Marie-Agnès
MA
Dillies
Institut Pasteur, Plate-forme Transcriptome Epigenome, Centre Innovation et Recherche Technologiques, Paris, France.
Caroline
C
Proux
Institut Pasteur, Plate-forme Transcriptome Epigenome, Centre Innovation et Recherche Technologiques, Paris, France.
Bernd
B
Jagla
Institut Pasteur, Plate-forme Transcriptome Epigenome, Centre Innovation et Recherche Technologiques, Paris, France.
Jean-Yves
JY
Coppée
INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France.
Olivier
O
Tabary
INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France; Pneumologie pédiatrique, AP-HP, Hôpital Trousseau, Paris, France.
Harriet
H
Corvol
INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France.
Michel
M
Chignard
INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France.
Loïc
L
Guillot
D000328:Adult; D001980:Bronchi / Q000382:microbiology* / Q000473:pathology; D003550:Cystic Fibrosis / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D004847:Epithelial Cells / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D011552:Pseudomonas Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa; D015533:Transcriptional Activation; D055815:Young Adult