Dectin-1 is expressed in human lung and mediates the proinflammatory immune response to nontypeable Haemophilus influenzae.
Dectin-1 is expressed in human lung and mediates the proinflammatory immune response to nontypeable Haemophilus influenzae.
复制标题
Dectin-1在人肺中表达，并介导对不可能的流感嗜血杆菌的促炎性免疫反应。
DOI：
10.1128/mbio.01492-14
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发表时间：
2014-08-26
期刊：
影响因子：
6.4
通讯作者：
Slevogt H
中科院分区：
文献类型：
--
作者：
Heyl KA;Klassert TE;Heinrich A;Müller MM;Klaile E;Dienemann H;Grünewald C;Bals R;Singer BB;Slevogt H
C型凝集素受体Dectin-1主要在骨髓细胞上表达，介导靶向呼吸道病原体如烟曲霉和结核分枝杆菌的免疫应答。肺上皮是这些病原体与呼吸道相互作用的重要界面。因此，我们分析了Dectin-1在人肺中的表达模式。免疫组织化学染色的人肺切片19人中有17人Dectin-1阳性，主要表达于支气管和肺泡上皮的顶端。我们的研究结果表明，与慢性阻塞性肺疾病（COPD）或吸烟习惯的患者没有相关性。不可分型流感嗜血杆菌（NTHI）是一种重要的呼吸道细菌病原体，在COPD中具有重要意义，也被认为是Dectin-1识别的，这表明可能对人类气道中NTHI依赖性免疫应答产生影响。因此，在原代正常人支气管上皮（NHBE）细胞和用Dectin-1稳定转染的A549细胞系中研究了Dectin-1参与NTHI触发的细胞因子应答。Dectin-1的存在显著增加了NHBE和A549细胞中响应NTHI的细胞因子释放。此外，Dectin-1 hem免疫受体酪氨酸激活基序（hemITAM）的磷酸化对于A549细胞中Dectin-1触发的对NTHI的反应是必不可少的。总之，在人类气道中，上皮表达的Dectin-1可能在产生NTHI介导的促炎症免疫反应中发挥重要作用。在这项研究中，我们证明，为第一次，Dectin-1的表达在人类肺组织，特别是肺上皮细胞，通过使用免疫组织化学染色。人类气道的上皮衬里是宿主-病原体相互作用的重要界面。因此，我们的数据表明，上皮表达的Dectin-1对于人类气道与通过该受体检测的病原体（例如烟曲霉和结核分枝杆菌）的相互作用具有相当重要的意义。此外，我们进一步证明，在肺上皮细胞中，Dectin-1增强了对NTHI的促炎免疫应答。在COPD患者中，NTHI是呼吸道感染的主要原因，并且与下呼吸道中的促炎性免疫应答相关。因此，我们的数据表明，Dectin-1与NTHI在人体气道中的功能相互作用可能对COPD的发病机制产生重要影响。
The C-type lectin receptor Dectin-1 is expressed mainly on myeloid cells mediating the immune response targeting respiratory pathogens such as Aspergillus fumigatus and Mycobacterium tuberculosis. The pulmonary epithelium serves as an important interface for interactions between these pathogens and the respiratory tract. Therefore, we analyzed the expression pattern of Dectin-1 in the human lung. Immunohistochemically stained human lung sections from 17 out of 19 individuals were positive for Dectin-1, which was expressed mainly apically on bronchial and alveolar epithelium. Our results showed no correlation with chronic obstructive pulmonary disease (COPD) or the smoking habits of the patients. Nontypeable Haemophilus influenzae (NTHI), an important bacterial pathogen of the respiratory tract with significant importance in COPD, has also been proposed to be recognized by Dectin-1, suggesting a possible impact on the NTHI-dependent immune response in human airways. Therefore, the involvement of Dectin-1 in NTHI-triggered cytokine responses was investigated in primary normal human bronchial epithelial (NHBE) cells and in the A549 cell line stably transfected with Dectin-1. The presence of Dectin-1 significantly increased cytokine release in response to NTHI in NHBE and A549 cells. In addition, phosphorylation of the Dectin-1 hem-immunoreceptor tyrosine-based activation motif (hemITAM) was essential for the Dectin-1-triggered response to NTHI in A549 cells. In conclusion, in human airways, epithelium-expressed Dectin-1 may play a significant role in generating an NTHI-mediated, proinflammatory immune response. In this study, we demonstrated, for the first time, the expression of Dectin-1 on human lung tissues and, in particular, pulmonary epithelium by making use of immunohistochemical staining. The epithelial lining of the human airways is an important interface for host-pathogen interactions. Therefore, our data suggest that epithelium-expressed Dectin-1 is of considerable importance for the interaction of the human airways with pathogens detected by this receptor, such as A. fumigatus and M. tuberculosis. Moreover, we further demonstrated that, in pulmonary epithelial cells, Dectin-1 enhances the proinflammatory immune response to NTHI. In COPD patients, NTHI is a major cause of respiratory tract infections and is associated with proinflammatory immune responses in the lower airways. Therefore, our data suggest that the functional interaction of Dectin-1 with NTHI in human airways may have an important impact on the pathogenesis of COPD.