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Infection and Immunity, May 2009, p. 2212-2220, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01224-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor β Signaling in the Epithelium{triangledown}

Christoph Beisswenger,1 Elena S. Lysenko,1 and Jeffrey N. Weiser1,2*

Departments of Microbiology,1 Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 191042

Received 6 October 2008/ Returned for modification 15 November 2008/ Accepted 22 February 2009

Colonization of the upper respiratory tract is an initial step that may lead to disease for many pathogens. To prevent compromise of the epithelial barrier, the host must monitor and tightly control bacterial levels on the mucosa. Here we show that innate immune functions of respiratory epithelial cells control colonization by Streptococcus pneumoniae and Haemophilus influenzae in a Toll-like receptor (TLR)-dependent manner. Activation of inflammatory pathways, including mitogen-activated protein kinase signaling, in respiratory epithelial cells was accompanied by the induction of the transforming growth factor β signaling cascade during early colonization. Thus, colonization resulted in upregulation of factors involved in a proinflammatory response (e.g., interleukin-6) as well as factors known to modulate the epithelial barrier (e.g., Snail-1). These in vivo data provided a link between inflammation control and maintenance of the mucosal barrier function during infection and emphasized the importance of TLR-dependent inflammatory responses of the respiratory epithelium.


* Corresponding author. Mailing address: 402A Johnson Pavilion, Department of Microbiology and Pediatrics, University of Pennsylvania, Philadelphia, PA 19104-6076. Phone: (215) 573-3511. Fax: (215) 573-4856. E-mail: weiser{at}mail.med.upenn.edu

{triangledown} Published ahead of print on 2 March 2009.

Editor: A. Camilli


Infection and Immunity, May 2009, p. 2212-2220, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01224-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.