Department of MIG, Division of Laboratory Medicine, Lund University, Lund, Sweden.
Immunobiology. 2013 Jul;218(7):984-94. doi: 10.1016/j.imbio.2012.11.001. Epub 2012 Nov 28.
The interaction between mycobacteria and epithelium is unexplored, but may determine the outcome of the infection. We have analyzed the role of two G protein-coupled receptors, CXCR1 and CXCR2 that are important regulators of many pulmonary diseases. We found that mycobacteria significantly increased the expression of both CXCR1 and CXCR2 on alveolar epithelial cells and both receptors were found to be important for neutrophil diapedesis across primary endothelial cells towards infected mucosa. Mycobacteria, lipoarabinomannan or 19-kDa glycolipoprotein up-regulated the inhibitory G protein-coupled receptor kinase (GRK)2, while GRK3 was less affected. Mycobacteria-induced GRK2 up-regulation decreased chemokine transcription and secretion thereby affecting the neutrophil recruitment to infected mucosa. These events were completely abolished by blocking these receptors prior to infection as the blocking increased epithelial immune responses. We have identified novel interactions occurring in the initial phase of mycobacterial infections by which mycobacterial manipulate epithelial inflammatory responses.
分枝杆菌与上皮细胞的相互作用尚不清楚，但可能决定感染的结果。我们分析了两个 G 蛋白偶联受体 CXCR1 和 CXCR2 的作用，它们是许多肺部疾病的重要调节剂。我们发现分枝杆菌显著增加了肺泡上皮细胞上的 CXCR1 和 CXCR2 的表达，并且这两个受体对于中性粒细胞穿过原发性内皮细胞向感染的粘膜迁移都是重要的。分枝杆菌、脂阿拉伯甘露聚糖或 19-kDa 糖脂都能上调抑制性 G 蛋白偶联受体激酶 (GRK)2，而 GRK3 的影响较小。分枝杆菌诱导的 GRK2 上调减少了趋化因子的转录和分泌，从而影响了中性粒细胞向感染粘膜的募集。在感染前阻断这些受体可以完全消除这些事件，因为阻断增加了上皮细胞的免疫反应。我们已经确定了分枝杆菌感染初始阶段发生的新的相互作用，分枝杆菌通过这些相互作用来操纵上皮细胞的炎症反应。
