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Dynamic interaction between airway epithelial cells and Staphylococcus aureus

¹Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S 514, Institut Fédératif de Recherche 53, Centre Hospitalier Universitaire Maison Blanche, 51092 Reims Cedex; ⁴Institut National de la Santé et de la Recherche Médicale Equipe Propre Inserm 0014, 54505 Vandoeuvre les Nancy, France; ²Institute of Microbiology Prof. Paulo de Góes, Federal University of Rio de Janeiro, 21-941-590 Rio de Janeiro; and ³Department of Microbiology and Immunology, State University of Rio de Janeiro, 20-551-030 Rio de Janeiro, Brazil

Submitted 23 July 2003 ; accepted in final form 8 May 2004

Staphylococcus aureus is a major cause of pulmonary infection, particularly in cystic fibrosis (CF) patients. However, few aspects of the interplay between S. aureus and host airway epithelial cells have been investigated thus far. We investigated by videomicroscopy the time- and bacterial concentration-dependent (10⁴, 10⁶, and 10⁸ CFU/ml) effect of S. aureus on adherence, internalization, and the associated damage of the airway epithelial cells. The balance between the secretion by S. aureus of the -toxin virulence factor and by the airway cells of the antibacterial secretory leukoproteinase inhibitor (SLPI) was also analyzed. After 1 h of interaction, whatever the initial bacterial concentration, a low percentage of S. aureus (<8%) adhered to airway cells, and no airway epithelial cell damage was observed. In contrast, after 24 h of incubation, more bacteria adhered to airway epithelial cells, internalized bacteria were observed, and a bacterial concentration-dependent effect on airway cell damage was observed. At 24 h, most airway cells incubated with bacteria at 10⁸ CFU/ml exhibited a necrotic phenotype. The necrosis was preceded by a transient apoptotic process. In parallel, we observed a time- and bacterial concentration-dependent decrease in SLPI and increase in -toxin expression. These results suggest that airway cells can defend against S. aureus in the early stages of infection. However, in later phases, there is a marked imbalance between the bactericidal capacity of host cells and bacterial virulence. These findings reinforce the potential importance of S. aureus in the pathogenicity of airway infections, including those observed early in CF patients.

videomicroscopy; secretory leukoproteinase inhibitor; -toxin; airway cell damage; bacterial adherence and internalization

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