Department Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
J Anat. 2013 May;222(5):495-503. doi: 10.1111/joa.12039. Epub 2013 Mar 22.
Toll-like receptors (TLR) recognize conserved molecular motifs of microorganisms, and constitute an important part of the innate immune system. Numerous studies have shown the importance of these receptors, including TLR9, in establishing effective immune responses to a broad range of infections, and in disorders such as COPD. TLR9 detects unmethylated DNA and is expressed in a wide range of immune cells in mice and humans, as well as other species. Most TLR9 expression studies have been done on cultured or isolated cells, but none that we know of on intact lung. Because cell-specific expression of TLR9 is important to understand its precise role in lung physiology, we tested mouse and human lung tissues for expression of TLR9 mRNA and protein with in situ hybridization and immunohistochemistry, respectively. We found TLR9 mRNA and protein expression in bronchial epithelium, vascular endothelium, alveolar septal cells and alveolar macrophages in both species. Immuno-electron microscopy delineated TLR9 expression in plasma membrane, cytoplasm and the nucleus of various lung cells. Lungs from human cases of COPD had significantly increased numbers of TLR9-positive cells. These are the first data showing TLR9 mRNA and protein expression in intact human and mouse lungs. The data may be useful for clarifying the role of TLR9 in the contributions of specific cells to lung physiology.
Toll 样受体 (TLR) 识别微生物的保守分子结构,是先天免疫系统的重要组成部分。大量研究表明,包括 TLR9 在内的这些受体在建立对广泛感染的有效免疫反应,以及在 COPD 等疾病中具有重要作用。TLR9 识别未甲基化的 DNA,并在小鼠和人类以及其他物种的多种免疫细胞中表达。大多数 TLR9 表达研究都是在培养或分离的细胞上进行的,但我们尚未在完整的肺组织上进行过此类研究。因为 TLR9 的细胞特异性表达对于理解其在肺生理学中的精确作用非常重要,所以我们使用原位杂交和免疫组织化学分别检测了小鼠和人肺组织中 TLR9 mRNA 和蛋白的表达。我们在两种物种的支气管上皮细胞、血管内皮细胞、肺泡间隔细胞和肺泡巨噬细胞中发现了 TLR9 mRNA 和蛋白的表达。免疫电子显微镜描绘了各种肺细胞中 TLR9 在质膜、细胞质和核中的表达。COPD 患者的肺组织中 TLR9 阳性细胞的数量显著增加。这是首次在完整的人类和小鼠肺组织中显示 TLR9 mRNA 和蛋白表达的研究。这些数据可能有助于阐明 TLR9 在特定细胞对肺生理学贡献中的作用。