Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Mol Immunol. 2012 Oct;52(3-4):183-9. doi: 10.1016/j.molimm.2012.05.014. Epub 2012 Jun 13.
The development of active tuberculosis after infection with Mycobacterium tuberculosis is almost invariably associated with a persistent or transient state of relative immunodeficiency. The receptor for advanced glycation end products (RAGE) is a promiscuous receptor that is involved in pulmonary inflammation and infection. To investigate the role of RAGE in tuberculosis, we intranasally infected wild-type (Wt) and RAGE deficient (RAGE(-/-)) mice with live virulent M. tuberculosis. While lungs of uninfected Wt mice expressed RAGE, in particular on endothelium, M. tuberculosis pneumonia was associated with an enhanced pulmonary expression of RAGE. Lung inflammation was increased in RAGE(-/-) mice, as indicated by histopathology, percentage of inflamed area, lung weight and cytokine and chemokine levels. In addition, lung lymphocyte and neutrophil numbers were increased in the RAGE(-/-) mice. RAGE(-/-) mice had modestly higher mycobacterial loads in the lungs after 3 weeks but not after 6 weeks of infection. Moreover, RAGE(-/-) mice displayed more body weight loss and enhanced mortality. In summary, pulmonary RAGE expression is increased during tuberculosis. In addition, these data suggest that RAGE plays a beneficial role in the host response to pulmonary tuberculosis.
结核分枝杆菌感染后发生活动性肺结核几乎总是与持续或短暂的相对免疫缺陷状态有关。晚期糖基化终产物受体（RAGE）是一种混杂的受体，参与肺部炎症和感染。为了研究 RAGE 在结核病中的作用，我们通过鼻腔感染野生型（Wt）和 RAGE 缺陷型（RAGE(-/-)）小鼠活的有毒结核分枝杆菌。虽然未感染的 Wt 小鼠的肺表达 RAGE，特别是在内皮细胞上，但结核分枝杆菌肺炎与肺中 RAGE 的表达增强有关。组织病理学、炎症区域百分比、肺重以及细胞因子和趋化因子水平表明，RAGE(-/-)小鼠的肺部炎症增加。此外，RAGE(-/-)小鼠的肺淋巴细胞和中性粒细胞数量增加。在感染后 3 周而非 6 周时，RAGE(-/-)小鼠的肺部分枝杆菌负荷略高。此外，RAGE(-/-)小鼠的体重减轻更多，死亡率更高。总之，在结核病期间肺中 RAGE 的表达增加。此外，这些数据表明 RAGE 在宿主对肺结核的反应中发挥有益作用。
