Schmausser B, Andrulis M, Endrich S, Lee S K, Josenhans C, Müller-Hermelink H-K, Eck M
Institut für Pathologie, Universität Würzburg, Wuerzburg, Germany.
Clin Exp Immunol. 2004 Jun;136(3):521-6. doi: 10.1111/j.1365-2249.2004.02464.x.
Toll-like receptors (TLRs) expressed by mucosal epithelium play an essential role in the defense against microbes by recognizing conserved bacterial molecules. For the first time TLR4, TLR5 and TLR9 have been microanatomically localized in patients with noninflamed gastric mucosa and Helicobacter pylori gastritis by immunohistochemistry. Because polarized expression of TLRs in apical and basolateral epithelial compartments is thought to modulate mucosal immunity, subcellular TLR distribution by gastric epithelium was investigated using confocal microscopy. TLR4, TLR5 and TLR9 were expressed by gastric epithelium in antrum and corpus of all patients with H. pylori gastritis (n = 14) and with noninflamed gastric mucosa (n = 5). TLR4 was expressed at the apical and the basolateral pole of the gastric epithelium as well in noninflamed gastric mucosa as in H. pylori gastritis. TLR5 and TLR9 expression in the noninflamed gastric mucosa was identical to that of TLR4 with localization at the apical and the basolateral epithelial pole. However, in H. pylori gastritis TLR5 and TLR9 expression on the gastric epithelium changed to an exclusive basolateral localization without detectable expression at the apical pole. In the human stomach, the gastric epithelium expressed TLR4, TLR5 and TLR9, which gives it the possibility to interact with H. pylori. Furthermore, gastric epithelial TLR4 expression is highly polarized in an apical and a basolateral compartment, whereas TLR5 and TLR9 polarization seems to be a process dynamically influenced by H. pylori infection. This polarized and dynamically regulated gastric epithelial expression of TLRs supports a sentinel role for these receptors in the mucosal immunity to H. pylori.
黏膜上皮表达的Toll样受体（TLRs）通过识别保守的细菌分子，在抵御微生物方面发挥着重要作用。首次通过免疫组织化学在非炎症性胃黏膜和幽门螺杆菌胃炎患者中对TLR4、TLR5和TLR9进行了微观解剖定位。由于TLRs在顶端和基底外侧上皮区室的极化表达被认为可调节黏膜免疫，因此使用共聚焦显微镜研究了胃上皮细胞亚细胞TLR的分布。所有幽门螺杆菌胃炎患者（n = 14）和非炎症性胃黏膜患者（n = 5）的胃窦和胃体上皮均表达TLR4、TLR5和TLR9。在非炎症性胃黏膜和幽门螺杆菌胃炎中，TLR4均表达于胃上皮的顶端和基底外侧极。非炎症性胃黏膜中TLR5和TLR9的表达与TLR4相同，定位于顶端和基底外侧上皮极。然而，在幽门螺杆菌胃炎中，胃上皮上TLR5和TLR9的表达转变为仅位于基底外侧，顶端未检测到表达。在人胃中，胃上皮表达TLR4、TLR5和TLR9，这使其有可能与幽门螺杆菌相互作用。此外，胃上皮TLR4的表达在顶端和基底外侧区室高度极化，而TLR5和TLR9的极化似乎是一个受幽门螺杆菌感染动态影响的过程。TLRs在胃上皮的这种极化和动态调节表达支持了这些受体在针对幽门螺杆菌的黏膜免疫中的哨兵作用。
