A species-specific activation of Toll-like receptor signaling in bovine and sheep bronchial epithelial cells triggered by Mycobacterial infections
A species-specific activation of Toll-like receptor signaling in bovine and sheep bronchial epithelial cells triggered by Mycobacterial infections
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DOI：
10.1016/j.molimm.2016.01.004
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发表时间：
2016-03-01
影响因子：
3.6
通讯作者：
Liu, Xiaoming
中科院分区：
文献类型：
--
作者：
Ma, Yan;Han, Fei;Liu, Xiaoming
由分枝杆菌感染引起的肺结核在世界大部分地区仍然是一个主要的公共卫生问题，部分原因是其病原体在包括人、家畜和野生动物在内的宿主之间的传播。迄今为止，结核病发病机制的分子机制仍不完全清楚。除了肺泡巨噬细胞，气道上皮细胞最近也被认为是分枝杆菌感染的主要靶点。为了解结核分枝杆菌与气道上皮细胞之间的病原-宿主相互作用，本研究采用原代气液界面（air-liquid interface，ALI）支气管上皮细胞培养模型，研究了结核分枝杆菌无毒力株H37 Ra和卡介苗（Mycobacterium bovis BCG）疫苗株感染后，牛和绵羊气道上皮细胞Toll样受体（Toll like receptor，TLR）信号转导的变化。我们的研究结果揭示了宿主和病原体物种特异性TLR介导的病原体相关分子模式（PAMPs）的识别，TLR信号通路的诱导和激活，以及支气管上皮细胞对这两个物种之间的分枝杆菌感染的炎症反应的实质性诱导。有趣的是，在牛支气管上皮细胞中，由分枝杆菌感染诱导的激活TLR信号转导主要是通过髓样分化因子88（MyD 88）非依赖性TLR信号转导途径，而在绵羊上皮细胞中，MyD 88依赖性和非依赖性TLR信号转导级联均可被诱导。同样值得注意的是，BCG感染能够在绵羊和牛气道上皮细胞中诱导MyD 88依赖性和独立性信号传导，但相对于牛，在绵羊上皮细胞中诱导了更强烈的炎症反应;而H37 Ra感染显示出在这两种宿主物种中主要触发MyD 88非依赖性TLR信号级联的能力，并诱导牛细胞中炎性细胞因子的表达。因此，这些数据为牛和绵羊气道上皮细胞对分枝杆菌感染的宿主和病原体种属特异性反应提供了证据，这也表明在解释使用主要宿主以外的种属生成的数据时需要考虑配体或病原体的功能作用或机制。(C)2016爱思唯尔有限公司版权所有
Pulmonary tuberculosis caused by a Mycobacterium infection remains a major public health problem in most part of the world, in part owing to the transmission of its pathogens between hosts including human, domestic and wild animals. To date, molecular mechanisms of the pathogenesis of TB are still incompletely understood. In addition to alveolar macrophages, airway epithelial cells have also been recently recognized as main targets for Mycobacteria infections. In an effort to understand the pathogen-host interaction between Mycobacteria and airway epithelial cells in domestic animals, in present study, we investigated the Toll-like receptor (TLR) signaling in bovine and sheep airway epithelial cells in response to an infection of Mycobacterium tuberculosis avirulent H37Ra stain or Mycobacterium bovis BCG vaccine strain, using primary air-liquid interface (ALI) bronchial epithelial culture models. Our results revealed a host and pathogen species-specific TLR-mediated recognition of pathogen-associated molecular patterns (PAMPs), induction and activation of TLR signaling pathways, and substantial induction of inflammatory response in bronchial epithelial cells in response to Mycobacteria infections between these two species. Interestingly, the activation TLR signaling in bovine bronchial epithelial cells induced by Mycobacteria infection was mainly through a myeloid differentiation factor 88 (MyD88)-independent TLR signaling pathway, while both MyD88-dependent and independent TLR signaling cascades could be induced in sheep epithelial cells. Equally noteworthy, a BCG infection was able to induce both MyD88-dependent and independent signaling in sheep and bovine airway epithelial cells, but more robust inflammatory responses were induced in sheep epithelial cells relative to the bovines; whereas an H37Ra infection displayed an ability to mainly trigger a MyD88-independent TLR signaling cascade in these two host species, and induce a more extent expression of inflammatory cytokines in bovine cells in comparison with that in sheep. These data thus provide an evidence for a host and pathogen species-specific response in bovine and sheep airway epithelial cells in response to Mycobacteria infections, which also suggest there is a need to consider in the interpretation of data generated using a species other than the primary host for analysis of a function role or mechanism of ligands or pathogens. (C) 2016 Elsevier Ltd. All rights reserved.