Mycobacterium tuberculosis-infected human macrophages exhibit enhanced cellular adhesion with increased expression of LFA-1 and ICAM-1 and reduced expression and/or function of complement receptors, FcγRII and the mannose receptor
Mycobacterium tuberculosis-infected human macrophages exhibit enhanced cellular adhesion with increased expression of LFA-1 and ICAM-1 and reduced expression and/or function of complement receptors, FcγRII and the mannose receptor
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DOI：
10.1099/00221287-148-10-3161
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发表时间：
2002-10-01
期刊：
影响因子：
2.8
通讯作者：
Schlesinger, LS
中科院分区：
文献类型：
--
作者：
DesJardin, LE;Kaufman, TM;Schlesinger, LS
结核分枝杆菌 (Mtb) 进入宿主巨噬细胞并在此环境中生存是结核病发病机制的关键组成部分。细菌在肺泡巨噬细胞内进行细胞内复制后，杆菌扩散到肺部区域淋巴结，随后将抗原呈递给宿主免疫系统。这一过程是如何发生的仍然知之甚少，但一种机制可能涉及含有 Mtb 的巨噬细胞穿过肺泡迁移到淋巴结，在淋巴结中出现保护性宿主反应，形成部分由聚集和融合、凋亡、感染的巨噬细胞组成的肉芽肿。白细胞整合素，包括淋巴细胞功能相关抗原 1 (LFA-1) 和补体受体 CR3 和 CR4，及其反受体在巨噬细胞粘附过程和吞噬作用中发挥重要作用。在这项研究中，使用反相显微镜和人单核细胞源性巨噬细胞 (MDM) 的体外培养模型检查了 Mtb 感染的巨噬细胞随时间的变化情况。在用 Mtb 感染 MDM 之前和之后，巨噬细胞在单层培养物中以单个细胞的形式出现；然而，在感染 Mtb 后 24 小时内，MDM 开始迁移并相互粘附。该反应的动力学取决于 m.o.i.以及感染的持续时间。定量透射电子显微镜研究表明，感染后 72 小时，巨噬细胞粘附伴随着 LFA-1 及其反受体 (ICAM-1) 水平的增加，吞噬细胞受体 CR3、CR4 和 FcgammaRII 表面水平的降低，以及主要组织相容性复合物 II 类 (MHC-II) 分子的增加。 CR3和CR4表面水平的降低具有功能相关性，含有活杆菌的巨噬细胞显示出对补体调理作用的绵羊红细胞的吞噬能力减弱；含有热灭活杆菌的巨噬细胞并未表现出这种能力的减弱。巨噬细胞粘附和吞噬蛋白的调节可能会影响宿主内 Mtb 感染的巨噬细胞的运输，LFA-1 和 ICAM-1 水平的增加增强了巨噬细胞的粘附特性，而吞噬细胞受体的减少则降低了已感染细胞的吞噬能力，可能有助于维持 Mtb 的细胞内生态位。 山地车。
The entry of Mycobacterium tuberculosis (Mtb) into the host macrophage and its survival in this environment are key components of tuberculosis pathogenesis. Following intracellular replication of the bacterium within alveolar macrophages, there is spread of bacilli to regional lymph nodes in the lungs and subsequent presentation of antigens to the host immune system. How this process occurs remains poorly understood, but one mechanism may involve the migration of macrophages containing Mtb across the alveoli to lymph nodes, where there is development of a protective host response with formation of granulomas composed in part of aggregated and fused, apoptotic, infected macrophages. Leukocyte integrins, including lymphocyte function-associated antigen-1 (LFA-1) and complement receptors CR3 and CR4, and their counter receptors play a major role in macrophage adhesion processes and phagocytosis. In this study, the appearance of Mtb-infected macrophages over time was examined, using inverted-phase microscopy and an in vitro culture model of human monocyte-derived macrophages (MDMs). Prior to and immediately following infection of the MDMs with Mtb, the macrophages appeared as individual cells in monolayer culture; however, within 24 h of infection with Mtb, the MDMs began to migrate and adhere to each other. The kinetics of this response were dependent on both the m.o.i. and the length of infection. Quantitative transmission electron microscopy studies revealed that macrophage adhesion was accompanied by increases in levels of LFA-1 and its counter receptor (ICAM-1), decreases in surface levels of the phagocytic receptors CR3, CR4 and FcgammaRII, and an increase in major histocompatibility complex Class II (MHC-II) molecules at 72 h post-infection. Decreases in surface levels of CR3 and CR4 had a functional correlate, with macrophages containing live bacilli showing a diminished phagocytic capacity for complement-opsonized sheep erythrocytes; macrophages containing heat-killed bacilli did not show this diminished capacity. The modulation of macrophage adhesion and phagocytic proteins may influence the trafficking of Mtb-infected macrophages within the host, with increases in levels of LFA-1 and ICAM-1 enhancing the adhesive properties of the macrophage and decreases in phagocytic receptors diminishing the phagocytic capacity of an already-infected cell, potentially allowing for maintenance of the intracellular niche of Mtb.