Klebsiella pneumoniae Capsule Polysaccharide Impedes the Expression of β-Defensins by Airway Epithelial Cells
Klebsiella pneumoniae Capsule Polysaccharide Impedes the Expression of β-Defensins by Airway Epithelial Cells
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DOI：
10.1128/iai.00940-09
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发表时间：
2010-03-01
影响因子：
3.1
通讯作者：
Bengoechea, Jose A.
中科院分区：
文献类型：
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作者：
Moranta, David;Regueiro, Veronica;Bengoechea, Jose A.
人类β -防御素（hBDs）有助于保护呼吸道免受病原体的侵害。我们有理由假设病原体已经发展出了抵抗它们的对策。肺炎克雷伯菌胶囊多糖（CPS）介导对hBD1和hBD2的耐药，而不是脂多糖O抗原。hBD3是对抗克雷伯菌最有效的hBD。我们研究了肺炎克雷伯菌作为肺部生存策略的可能性，它可能不会激活hBDs的表达。用CPS突变体52145-Delta wca（K2）感染A549和正常人支气管细胞后，hBD2和hBD3的表达增加。野生型和脂多糖O抗原突变体均未增加hBDs的表达。在体内，52145-Delta wca（K2）比野生型诱导更高水平的mBD4和mBD14，分别是hBD2和hBD3的可能的小鼠同源物。52145-Delta wca（K2）依赖性hBD2的上调通过NF-kappa B和丝裂原活化蛋白激酶（MAPKs） p44/42、Jun n-末端蛋白激酶（JNK）依赖性途径发生。hBD3表达的增加依赖于MAPK - JNK。52145-Delta wca（K2）通过toll样受体2和4 （TLR2和TLR4）激活hBD2，而hBD3的表达依赖于NOD1。肺炎克雷伯菌诱导CYLD和MKP-1的表达，它们是52145-Delta wca（K2）诱导的hBDs表达的负调控因子。模式识别受体的细菌参与诱导CYLD和MKP-1，这可能启动促炎途径的衰减。本研究结果表明，肺炎克雷伯菌CPS不仅可以保护病原体免受防御素的杀菌作用，还可以抑制防御素的表达。肺炎克雷伯菌CPS的这些特征可能有助于病原体在肺部的恶劣环境中生存。
Human beta-defensins (hBDs) contribute to the protection of the respiratory tract against pathogens. It is reasonable to postulate that pathogens have developed countermeasures to resist them. Klebsiella pneumoniae capsule polysaccharide (CPS), but not the lipopolysaccharide O antigen, mediated resistance against hBD1 and hBD2. hBD3 was the most potent hBD against Klebsiella. We investigated the possibility that as a strategy for survival in the lung, K. pneumoniae may not activate the expression of hBDs. Infection of A549 and normal human bronchial cells with 52145-Delta wca(K2), a CPS mutant, increased the expression of hBD2 and hBD3. Neither the wild type nor the lipopolysaccharide O antigen mutant increased the expression of hBDs. In vivo, 52145-Delta wca(K2) induced higher levels of mBD4 and mBD14, possible mouse orthologues of hBD2 and hBD3, respectively, than the wild type. 52145-Delta wca(K2)-dependent upregulation of hBD2 occurred via NF-kappa B and mitogen-activated protein kinases (MAPKs) p44/42, Jun N-terminal protein kinase (JNK)-dependent pathways. The increase in hBD3 expression was dependent on the MAPK JNK. 52145-Delta wca(K2) engaged Toll-like receptors 2 and 4 (TLR2 and TLR4) to activate hBD2, whereas hBD3 expression was dependent on NOD1. K. pneumoniae induced the expression of CYLD and MKP-1, which act as negative regulators for 52145-Delta wca(K2)-induced expression of hBDs. Bacterial engagement of pattern recognition receptors induced CYLD and MKP-1, which may initiate the attenuation of proinflammatory pathways. The results of this study indicate that K. pneumoniae CPS not only protects the pathogen from the bactericidal action of defensins but also impedes their expression. These features of K. pneumoniae CPS may facilitate pathogen survival in the hostile environment of the lung.