Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria
Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria
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DOI：
10.1165/rcmb.2017-0218oc
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发表时间：
2018-02-01
影响因子：
6.4
通讯作者：
Holland, Steven M.
中科院分区：
文献类型：
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作者：
Matsuyama, Masashi;Martins, Andrew J.;Holland, Steven M.
肺非结核分枝杆菌（NTM）病的发病率正在增加，但NTM感染呼吸道上皮的宿主反应尚未完全了解。在这项工作中，我们的目的是确定NTM感染的呼吸道上皮感染相关的基因表达特征。我们感染的空气-液体界面（ALI）的原代呼吸道上皮细胞培养与鸟分枝杆菌亚种。禽分枝杆菌（MAC）或分枝杆菌亚种（Mycobacterium canceressus subsp.）（MAB）.我们使用来自四个不同供体的细胞来获得可推广的数据。用MAC或MAB以100：1或1，000：1的感染复数感染ALI处的分化的呼吸道上皮细胞，并在感染后第1天和第3天进行RNA测序。在对感染的反应中，我们发现纤毛基因下调，但与细胞因子/趋化因子相关的基因上调，如IL-32和胆固醇生物合成。MAB比MAC感染更容易上调炎症反应基因。NTM在ALI的原发性呼吸道上皮细胞感染鉴定出纤毛功能、胆固醇生物合成和细胞因子/趋化因子产生是宿主对感染的主要反应。这些途径中的一些可能适合于治疗操作。
The incidence of pulmonary nontuberculous mycobacteria (NTM) disease is increasing, but host responses in respiratory epithelium infected with NTM are not fully understood. In this work, we aimed to identify infection-relevant gene expression signatures of NTM infection of the respiratory epithelium. We infected air-liquid interface (ALI) primary respiratory epithelial cell cultures with Mycobacterium avium subsp. avium (MAC) or Mycobacterium abscessus subsp. abscessus (MAB). We used cells from four different donors to obtain generalizable data. Differentiated respiratory epithelial cells at the ALI were infected with MAC or MAB at a multiplicity of infection of 100:1 or 1,000:1, and RNA sequencing was performed at Days 1 and 3 after infection. In response to infection, we found down-regulation of ciliary genes but upregulation of genes associated with cytokines/chemokines, such as IL-32, and cholesterol biosynthesis. Inflammatory response genes tended to be more upregulated by MAB than by MAC infection. Primary respiratory epithelial cell infection with NTM at the ALI identified ciliary function, cholesterol biosynthesis, and cytokine/chemokine production as major host responses to infection. Some of these pathways may be amenable to therapeutic manipulation.