SPLUNC1/BPIFA1 Contributes to Pulmonary Host Defense against Klebsiella pneumoniae Respiratory Infection
SPLUNC1/BPIFA1 Contributes to Pulmonary Host Defense against Klebsiella pneumoniae Respiratory Infection
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DOI：
10.1016/j.ajpath.2013.01.050
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发表时间：
2013-05-01
影响因子：
6
通讯作者：
Di, Y. Peter
中科院分区：
文献类型：
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作者：
Liu, Yang;Bartlett, Jennifer A.;Di, Y. Peter
上皮细胞宿主防御蛋白是肺对感染的先天免疫应答的重要组成部分。短腭、肺、鼻上皮克隆（PLP 1）1（SPLUNC 1）蛋白是含杀菌/通透性增加（BPI）折叠（BPIF）蛋白家族的成员，与BPI样蛋白共享结构相似性。SPLUNC 1是在鼻、口咽和肺上皮中表达的25 kDa分泌性蛋白，并且已经涉及针对铜绿假单胞菌和其他生物体的气道宿主防御。据报道SPLUNC 1具有表面活性剂性质，这可能有助于抗生物膜防御。本研究的目的是评估SPLUNC 1表面活性剂活性在气道上皮分泌物中的重要性，并探讨其在细菌感染模型中的生物学相关性。使用培养的气道上皮细胞，我们证实SPLUNC 1对于维持气道液体中的低表面张力至关重要。此外，我们证明重组SPLUNC 1（rSPLUNC 1）显着抑制肺炎克雷伯菌生物膜形成的气道上皮细胞。我们随后发现Splunc 1（-/-）小鼠对K. pneumoniae，证实了这种抗生物膜作用的可能体内相关性。我们的数据表明，SPLUNC 1是一个重要的组成部分，粘膜先天免疫防御肺部感染的相关气道病原体，并提供了进一步的支持，新的假设，SPLUNC 1蛋白防止细菌生物膜的形成，通过其调节气道液体的表面张力的能力。
Epithelial host defense proteins comprise a critical component of the pulmonary innate immune response to infection. The short palate, Lung, nasal epithelium clone (PLUNC) 1 (SPLUNC1) protein is a member of the bactericidal/permeability-increasing (BPI) fold-containing (BPIF) protein family, sharing structural similarities with BPI-like proteins. SPLUNC1 is a 25 kDa secretory protein that is expressed in nasal, oropharyngeal, and Lung epithelia, and has been implicated in airway host defense against Pseudomonas aeruginosa and other organisms. SPLUNC1 is reported to have surfactant properties, which may contribute to anti-biofilm defenses. The objective of this study was to assess the importance of SPLUNC1 surfactant activity in airway epithelial secretions and to explore its biological relevance in the context of a bacterial infection model. Using cultured airway epithelia, we confirmed that SPLUNC1 is critically important for maintenance of low surface tension in airway fluids. Furthermore, we demonstrated that recombinant SPLUNC1 (rSPLUNC1) significantly inhibited Klebsiella pneumoniae biofilm formation on airway epithelia. We subsequently found that Splunc1(-/-) mice were significantly more susceptible to infection with K. pneumoniae, confirming the Likely in vivo relevance of this anti-biofilm effect. Our data indicate that SPLUNC1 is a crucial component of mucosal innate immune defense against pulmonary infection by a relevant airway pathogen, and provide further support for the novel hypothesis that SPLUNC1 protein prevents bacterial biofilm formation through its ability to modulate surface tension of airway fluids.