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Physiol. Genomics 20: 244-255, 2005. First published December 14, 2004; doi:10.1152/physiolgenomics.00135.2004 Free Article
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Received 10 June 2004; accepted in final form 9 December 2004.
Physiological Genomics 20:244-255 (2005)
1094-8341/05 $5.00 © 2005 American Physiological Society

Live Staphylococcus aureus and bacterial soluble factors induce different transcriptional responses in human airway cells

Chimène Moreilhon1, Delphine Gras2, Coralie Hologne2, Odile Bajolet2, Françoise Cottrez3, Virginie Magnone1, Marc Merten4, Hervé Groux3, Edith Puchelle2 and Pascal Barbry1

1 Institut de Pharmacologie Moléculaire et Cellulaire UMR 6097 Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Valbonne
2 Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S 514, IFR 53, CHU Hôpital Maison Blanche, Reims
3 INSERM U576, Hôpital de l’Archet, Nice
4 INSERM EMI 10014, Vandoeuvre-les-Nancy, France

To characterize the response of respiratory epithelium to infection by Staphylococcus aureus (S. aureus), human airway cells were incubated for 1 to 24 h with a supernatant of a S. aureus culture (bacterial supernatant), then profiled with a pangenomic DNA microarray. Because an upregulation of many genes was noticed around 3 h, three independent approaches were then used to characterize the host response to a 3-h contact either with bacterial supernatant or with live bacteria: 1) a DNA microarray containing 4,200 sequence-verified probes, 2) a semiquantitative RT-PCR with a set of 537 pairs of validated primers, or 3) ELISA assay of IL-8, IL-6, TNF{alpha}, and PGE2. Among others, Fos, Jun, and EGR-1 were upregulated by the bacterial supernatant and by live bacteria. Increased expression of bhlhb2 and Mig-6, promoter regions which harbor HIF responding elements, was explained by an increased expression of the HIF-1{alpha} protein. Activation of the inducible form of cyclooxygenase, COX-2, and of the interleukins IL-1, IL-6, and IL-8, as well as of the NF-{kappa}B pathway, was observed preferentially in cells in contact with bacterial supernatant. Early infection was characterized by an upregulation of anti-apoptotic genes and a downregulation of pro-apoptotic genes. This correlated with a necrotic, rather than apoptotic cell death. Overall, this first global description of an airway epithelial infection by S. aureus demonstrates a larger global response to bacterial supernatant (in term of altered genes and variation factors) than to exponentially growing live bacteria.

transcriptome; microarray; inflammation; infection




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