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* Department of Medical Microbiology and Hygiene, University Heidelberg, Heidelberg, Germany;
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany;
Biochemical Pharmacology, University of Konstanz, Konstanz, Germany; and
Department of Internal Medicine, Division for Pulmonary Diseases, Philipps-University Marburg, Marburg, Germany
Bronchial epithelial cells represent the first line of defense against invading airborne pathogens. They are important contributors to innate mucosal immunity and provide a variety of antimicrobial effectors. However, mucosal surfaces are prone to contact with pathogenic, as well as nonpathogenic microbes, and therefore, immune recognition principles have to be tightly controlled to avoid uncontrolled permanent activation. TLRs have been shown to recognize conserved microbial patterns and to mediate inducible activation of innate immunity. Our experiments demonstrate that bronchial epithelial cells express functional TLR1–6 and TLR9 and thus make use of a common principle of professional innate immune cells. Although it was observed that TLR2 ligands dependent on heterodimeric signaling either with TLR1 or TLR6 were functional, other ligands like lipoteichoic acid were not. Additionally, it was found that bronchial epithelial cells could be stimulated only marginally by Gram-positive bacteria bearing known TLR2 ligands while Gram-negative bacteria were easily recognized. This correlated with low expression of TLR2 and the missing expression of the coreceptor CD36. Transgenic expression of both receptors restored responsiveness to the complete set of TLR2 ligands and Staphylococcus aureus. Additional gene-array experiments confirmed hyporesponsiveness to this bacterium while Pseudomonas aeruginosa and respiratory syncytial virus induced common, as well as pathogen-specific, sets of genes. The findings indicate that bronchial epithelium regulates its sensitivity to recognize microbes by managing receptor expression levels. This could serve the special needs of controlled microbial recognition in mucosal compartments.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This project was supported by grants of the Deutsche Forschungsgemeinschaft to A.H.D. (DFG Da 592/1 and /2) and R.B. (DFG 1641/6). The Microarray and Bioinformatics Core Unit at the Institute of Medical Microbiology, Immunology and Hygiene is supported in part by the Bundesministerium für Bildung und Forschung National Genome Research Network Infection and Inflammation FKZ 01GS0402, TP 37 to R.L.).
2 Address correspondence and reprint requests to Dr. Alexander H. Dalpke, Department of Medical Microbiology and Hygiene, Hygiene-Institute, University Heidelberg, Im Neuenheimer Feld 324, Heidelberg, Germany. E-mail address: alexander.dalpke{at}med.uni-heidelberg.de
3 Abbreviations used in this paper: LTA, lipoteichoic acid; MDP, muramyl dipeptide; MOI, multiplicity of infection; RSV, respiratory syncytial virus; DAP, diaminopimelic acid; P2C, Pam2CysSK4; P3C, Pam3CysSK4 pI:C, poly(deoxyinosinic-deoxycytidylic acid); PRR, pattern recognition receptors.
4 The online version of this article contains supplemental material.
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