Suppression of NF-κB-mediated β-defensin gene expression in the mammalian airway by the Bordetella type III secretion system

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Abstract
Expression of innate immune genes such as β‐defensins is induced in airway epithelium by bacterial components via activation of NF‐κB. We show here that live Gram‐negative bacteria can similarly stimulate this pathway, resulting in upregulation of the β‐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‐κB 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‐κB 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.