title: Differential recognition of TLR-dependent microbial ligands in human bronchial epithelial cells.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Hygiene, University Heidelberg, Im Neuenheimer Feld 324, Heidelberg, Germany.
authors.forename: Anja K
authors.initials: AK
authors.lastname: Mayer
authors.forename: Mario
authors.initials: M
authors.lastname: Muehmer
authors.forename: Jörg
authors.initials: J
authors.lastname: Mages
authors.forename: Katja
authors.initials: K
authors.lastname: Gueinzius
authors.forename: Christian
authors.initials: C
authors.lastname: Hess
authors.forename: Klaus
authors.initials: K
authors.lastname: Heeg
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Dalpke
mesh_terms: D000818:Animals; D001980:Bronchi / Q000276:immunology*; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology*; D051193:Toll-Like Receptors / Q000172:deficiency / Q000276:immunology*
chemical_list: D018955:CD36 Antigens; D008024:Ligands; D051193:Toll-Like Receptors