The Impact of CC16 on Pulmonary Epithelial-Driven Host Responses during Mycoplasma pneumoniae Infection in Mouse Tracheal Epithelial Cells.

The Impact of CC16 on Pulmonary Epithelial-Driven Host Responses during Mycoplasma pneumoniae Infection in Mouse Tracheal Epithelial Cells.
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在小鼠气管上皮细胞中肺炎支原体感染期间,克拉拉细胞蛋白16(CC16)对肺上皮驱动的宿主反应的影响

DOI:
10.3390/cells12151984
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发表时间:
2023-08-01
期刊:
影响因子:
6
通讯作者:
Ledford, Julie G. G.
Ledford, Julie G. G.
中科院分区:
生物学2区
文献类型:
--
作者:
Iannuzo, Natalie;Dy, Alane Blythe C.;Guerra, Stefano;Langlais, Paul R. R.;Ledford, Julie G. G.

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俱乐部细胞分泌蛋白(CC 16)在肺内起着许多保护作用;然而,完整的生物学功能,特别是在感染期间关于肺上皮的功能,仍然不清楚。我们之前已经表明,CC 16缺陷型(CC 16 −/−)小鼠气管上皮细胞(MTEC)与CC 16充足型(WT)MTEC相比,Mp负荷增加;因此,在这项研究中,我们希望进一步确定在CC 16缺陷的背景下,肺上皮如何对感染作出反应。使用质谱和定量蛋白质组学分析从在气-液界面生长的MTEC顶部分泌的蛋白质,我们研究了在肺炎支原体(MP)感染期间CC 16在肺上皮内的保护作用。当用Mp攻击时,WT MTEC的顶端蛋白分泌总体减少,而CC 16 −/− MTEC的顶端蛋白分泌与未攻击的对照相比增加。根据基因本体论和京都基因和基因组百科全书(KEGG)评估,CC 16 −/− MTEC(未激发和Mp感染期间)上调的许多蛋白质与气道重塑相关,而WT MTEC未观察到。这些研究结果表明,CC 16可能是重要的,在呼吸道感染MP,这是社区获得性肺炎的主要病原体肺上皮内提供保护。
Club Cell Secretory Protein (CC16) plays many protective roles within the lung; however, the complete biological functions, especially regarding the pulmonary epithelium during infection, remain undefined. We have previously shown that CC16-deficient (CC16−/−) mouse tracheal epithelial cells (MTECs) have enhanced Mp burden compared to CC16-sufficient (WT) MTECs; therefore, in this study, we wanted to further define how the pulmonary epithelium responds to infection in the context of CC16 deficiency. Using mass spectrometry and quantitative proteomics to analyze proteins secreted apically from MTECs grown at an air–liquid interface, we investigated the protective effects that CC16 elicits within the pulmonary epithelium during Mycoplasma pneumoniae (Mp) infection. When challenged with Mp, WT MTECs have an overall reduction in apical protein secretion, whereas CC16−/− MTECs have increased apical protein secretion compared to their unchallenged controls. Following Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessment, many of the proteins upregulated from CC16−/− MTECS (unchallenged and during Mp infection) were related to airway remodeling, which were not observed by WT MTECs. These findings suggest that CC16 may be important in providing protection within the pulmonary epithelium during respiratory infection with Mp, which is the major causative agent of community-acquired pneumoniae.
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