Suppression of NF-κB-mediated β-defensin gene expression in the mammalian airway by the Bordetella type III secretion system
Suppression of NF-κB-mediated β-defensin gene expression in the mammalian airway by the Bordetella type III secretion system
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DOI：
10.1111/j.1462-5822.2004.00473.x
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发表时间：
2005-04-01
影响因子：
3.4
通讯作者：
Diamond, G
中科院分区：
文献类型：
--
作者：
Legarda, D;Klein-Patel, ME;Diamond, G
天然免疫基因如β-防御素的表达在气道上皮中由细菌组分通过NF-κ B的活化诱导。我们在这里表明，活革兰氏阴性菌可以类似地刺激这一途径，导致上调β-防御素气管抗菌肽（TAP）在原代培养的牛气管上皮细胞（TEC），Toll样受体4（TLR 4）介导的途径。革兰氏阴性气道病原体支气管败血波氏杆菌具有III型分泌系统，先前通过免疫组织化学表明其抑制细胞系中NF-κ B的核转位。因此，我们假设这种病原体可能会干扰上皮细胞的先天免疫反应。TEC暴露于野生型B。支气管败血症抑制NF-κ B B的活化和随后TAP mRNA水平的诱导，而III型分泌缺陷型菌株则没有。这些结果表明，气道中的先天免疫应答的细菌逃避机制，这可能允许观察到的这种病原体的持续定植。
Expression of innate immune genes such as beta-defensins is induced in airway epithelium by bacterial components via activation of NF-kappa B. 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-kappa B 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-kappa B 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.