Foamy macrophages within lung granulomas of mice infected with Mycobacterium tuberculosis express molecules characteristic of dendritic cells and antiapoptotic markers of the TNF receptor-associated factor family
Foamy macrophages within lung granulomas of mice infected with Mycobacterium tuberculosis express molecules characteristic of dendritic cells and antiapoptotic markers of the TNF receptor-associated factor family
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DOI：
10.4049/jimmunol.175.6.3873
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发表时间：
2005-09-15
影响因子：
4.4
通讯作者：
Gonzalez-Juarrero, M
中科院分区：
文献类型：
--
作者：
Ordway, D;Henao-Tamayo, M;Gonzalez-Juarrero, M
高度空泡或泡沫巨噬细胞是感染结核分枝杆菌的动物肺部肉芽肿的明显特征。到目前为止，这些细胞通常被认为是从血液进入病变的单核细胞所产生的激活的巨噬细胞。然而，我们在这项研究中证明，泡沫巨噬细胞表达高水平的DEC-205，这是树突状细胞(DC)的标志特征。除了高表达DEC-205标记物外，这些细胞还被鉴定为CD11b+CD11c(高)、MHC类II高和CD40(高)，这是DC通常表达的额外标记物。CD40表达上调仅见于慢性肺部疾病早期，随着疾病进展到慢性晚期，CD40和MHC-II类标志物表达均下调。DEC-205标记阳性的泡沫细胞也表达高水平的TNFR相关因子-1(TRAF-1)、TRAF-2和TRAF-3，这些与抗凋亡相关的标记。这些数据表明，除了DC在启动针对结核分枝杆菌感染的获得性免疫反应中的核心作用外，它们还参与了肉芽肿性反应。
Highly vacuolated or foamy macrophages are a distinct characteristic of granulomas in the lungs of animals infected with Mycobacterium tuberculosis. To date these have usually been considered to represent activated macrophages derived from monocytes entering the lesions from the blood. However, we demonstrate in this study that foamy macrophages express high levels of DEC-205, a marker characteristic of dendritic cells (DCs). In addition to high expression of the DEC-205 marker, these cells were characterized as CD11b+CD11c(high)MHC class IIhigh, and CD40(high), which are additional markers typically expressed by DCs. Up-regulation of CD40 was seen only during the early chronic stage of the lung disease, and both the expression of CD40 and MHC class II markers were down-regulated as the disease progressed into the late chronic phase. Foamy cells positive for the DEC-205 marker also expressed high levels of TNFR-associated factor-1 (TRAF-1), TRAF-2, and TRAF-3, markers associated with resistance to apoptosis. These data indicate that in addition to the central role of DCs in initiating the acquired immune response against M. tuberculosis infection, they also participate in the granulomatous response.