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Infection and Immunity, February 2009, p. 714-724, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.00852-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Klebsiella pneumoniae Increases the Levels of Toll-Like Receptors 2 and 4 in Human Airway Epithelial Cells{triangledown}

Verónica Regueiro,1,2 David Moranta,1,2 Miguel A. Campos,1 Javier Margareto,3 Junkal Garmendia,1,2 and José A. Bengoechea1,2,4*

Program in Infection and Immunity, Fundació Caubet-CIMERA Illes Balears,1 Area Molecular Basis of Microbial Pathogenesis, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CibeRes), Bunyola, Spain,2 Unidad de Genómica, LEIA-Salud, Miñano, Spain,3 Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain4

Received 10 July 2008/ Returned for modification 7 August 2008/ Accepted 4 November 2008

Airway epithelial cells act as the first barrier against pathogens. These cells recognize conserved structural motifs expressed by microbial pathogens via Toll-like receptors (TLRs) expressed on the surface. In contrast to the level of expression in lymphoid cells, the level of expression of TLR2 and TLR4 in airway epithelial cells is low under physiological conditions. Here we explored whether Klebsiella pneumoniae upregulates the expression of TLRs in human airway epithelial cells. We found that the expression of TLR2 and TLR4 by A549 cells and human primary airway cells was upregulated upon infection with K. pneumoniae. The increased expression of TLRs resulted in enhancement of the cellular response upon stimulation with Pam3CSK4 and lipopolysaccharide, which are TLR2 and TLR4 agonists, respectively. Klebsiella-dependent upregulation of TLR expression occurred via a positive I{kappa}B{alpha}-dependent NF-{kappa}B pathway and via negative p38 and p44/42 mitogen-activated protein kinase-dependent pathways. We showed that Klebsiella-induced TLR2 and TLR4 upregulation was dependent on TLR activation. An isogenic capsule polysaccharide (CPS) mutant did not increase TLR2 and TLR4 expression. Purified CPS upregulated TLR2 and TLR4 expression, and polymyxin B did not abrogate CPS-induced TLR upregulation. Although no proteins were detected in the CPS preparation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and colloidal gold staining, we could not rule out the possibility that traces of protein in our CPS preparation could have been responsible, at least in part, for the TLR upregulation.

* Corresponding author. Mailing address: Fundació Caubet-CIMERA Illes Balears, Recinto Hospital Joan March, Carretera Soller Km 12, 07110 Bunyola, Spain. Phone: 34 971 011780. Fax: 34 971 011797. E-mail: bengoechea{at}caubet-cimera.es

{triangledown} Published ahead of print on 17 November 2008.

Editor: J. N. Weiser

Infection and Immunity, February 2009, p. 714-724, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.00852-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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