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Defensin-2 1
* Division of Dermatology,
Will Rogers Institute Pulmonary Research Laboratories,
Department of Microbiology and Immunology and Molecular Biology Institute, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095;
Department of Medicine, Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599;
¶ EMC Microcollections GmbH, Tubingen, Germany; and
|| Genentech Incorporated, South San Francisco, CA 94080
As pattern recognition receptors capable of eliciting responses to a diverse array of microbial products, Toll-like receptors (TLRs) participate in the activation of host defense mechanisms that protect against infectious pathogens. Given that epithelial cells lie at the interface between the host and its environment, we designed experiments to determine whether human airway epithelial cells express TLRs and respond to TLR agonists. Immunohistochemical labeling of TLR2 in normal human airways revealed TLR2 expression throughout the epithelium, with an apparently higher level of expression on noncolumnar basal epithelial cells. Two-color immunofluorescent labeling of TLR2 and cytokeratins 8 and 15 revealed that TLR2 is coexpressed with the epithelial cell markers. In addition, airway epithelial cells grown at air-liquid interface responded to bacterial lipopeptide in a TLR2-dependent manner with induction of mRNA and protein of the antimicrobial peptide human 
defensin-2. Stimulation of epithelial cell cultures with lipopeptide resulted in a small and variable reduction of bacteria on the apical surface. Together, these data suggest that TLRs monitor epithelial surfaces to enhance host defense by inducing the production of an antimicrobial peptide.
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