Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2.
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 beta 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.
Hertz
Cheryl J
CJ
Division of Dermatology, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Wu
Qi
Q
Porter
Edith Martin
EM
Zhang
Yan J
YJ
Weismüller
Karl-Heinz
KH
Godowski
Paul J
PJ
Ganz
Tomas
T
Randell
Scott H
SH
Modlin
Robert L
RL
D015415:Biomarkers / Q000032:analysis; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D015536:Down-Regulation / Q000502:physiology; D004926:Escherichia coli / Q000254:growth & development; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis; D008074:Lipoproteins / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000254:growth & development; D011956:Receptors, Cell Surface / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D013499:Surface Properties; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014132:Trachea / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D023083:beta-Defensins / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology
D015415:Biomarkers; C106641:DEFB4A protein, human; D016209:Interleukin-8; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D023083:beta-Defensins