Suppression of NF-kappaB-mediated beta-defensin gene expression in the mammalian airway by the Bordetella type III secretion system.
Expression of innate immune genes such as beta-defensins is induced in airway epithelium by bacterial components via activation of NF-kappaB. We show here that live Gram-negative bacteria can similarly stimulate this pathway, resulting in upregulation of the beta-defensin tracheal antimicrobial peptide (TAP) in primary cultures of bovine tracheal epithelial cells (TECs), by a Toll-like receptor 4 (TLR4)-mediated pathway. The Gram-negative airway pathogen Bordetella bronchiseptica possesses a type III secretion system previously suggested to inhibit the nuclear translocation of NF-kappaB in a cell line by immunohistochemistry. We therefore hypothesized that this pathogen might interfere in the innate immune response of the epithelium. Exposure of TECs to wild-type B. bronchiseptica suppressed the activation of NF-kappaB and the subsequent induction of TAP mRNA levels, whereas a type III secretion-defective strain did not. These results suggest a mechanism for bacterial evasion of the innate immune response in the airway, which could allow for the observed persistent colonization of this pathogen.
Legarda
Diana
D
Department of Oral Biology, UMDNJ - New Jersey Dental School, Newark, NJ, USA.
Klein-Patel
Marcia E
ME
Yim
Sunghan
S
Yuk
Ming H
MH
Diamond
Gill
G
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D016950:Bordetella bronchiseptica / Q000472:pathogenicity*; D002417:Cattle; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014132:Trachea / Q000166:cytology / Q000382:microbiology*; D015854:Up-Regulation; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D023083:beta-Defensins; C068629:tracheal antimicrobial peptide, bovine