The Mannose Receptor Is Involved in the Phagocytosis of Mycobacteria-Induced Apoptotic Cells.
The Mannose Receptor Is Involved in the Phagocytosis of Mycobacteria-Induced Apoptotic Cells.
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DOI：
10.1155/2016/3845247
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发表时间：
2016
影响因子：
4.1
通讯作者：
Mancilla R
中科院分区：
文献类型：
--
作者：
Garcia-Aguilar T;Espinosa-Cueto P;Magallanes-Puebla A;Mancilla R
结核分枝杆菌感染后，巨噬细胞可能会发生凋亡，这被认为是先天免疫反应。稳态细胞凋亡中死亡细胞去除的途径已被广泛研究，但对于分枝杆菌感染期间经历细胞凋亡的细胞如何被去除知之甚少。这项研究表明，用分枝杆菌细胞壁蛋白诱导发生凋亡的巨噬细胞通过甘露糖受体被 J-774A.1 单核细胞吞噬。该演示是通过用阻断性抗甘露糖受体抗体和甘露糖受体竞争剂糖抑制吞噬作用的测定来实现的。此外，通过特异性siRNA消除甘露糖受体显着降低了甘露糖受体的表达和凋亡细胞的吞噬作用。免疫荧光显示，被吞噬的凋亡小体最初位于 Rab5 阳性吞噬体中，该吞噬体成熟后表达吞噬溶酶体标记物 LAMP1。死亡细胞的吞噬作用引发抗炎反应，产生 TGF-β 和 IL-10，但不产生促炎细胞因子 IL-12 和 TNF-α。这项研究记录了先前未报道的甘露糖受体在结核病 (TB) 感染情况下参与清除凋亡细胞的过程。这些结果挑战了结核病中凋亡细胞吞噬作用具有免疫原性作用的观点。
Upon Mycobacterium tuberculosis infection, macrophages may undergo apoptosis, which has been considered an innate immune response. The pathways underlying the removal of dead cells in homeostatic apoptosis have been extensively studied, but little is known regarding how cells that undergo apoptotic death during mycobacterial infection are removed. This study shows that macrophages induced to undergo apoptosis with mycobacteria cell wall proteins are engulfed by J-774A.1 monocytic cells through the mannose receptor. This demonstration was achieved through assays in which phagocytosis was inhibited with a blocking anti-mannose receptor antibody and with mannose receptor competitor sugars. Moreover, elimination of the mannose receptor by a specific siRNA significantly diminished the expression of the mannose receptor and the phagocytosis of apoptotic cells. As shown by immunofluorescence, engulfed apoptotic bodies are initially located in Rab5-positive phagosomes, which mature to express the phagolysosome marker LAMP1. The phagocytosis of dead cells triggered an anti-inflammatory response with the production of TGF-β and IL-10 but not of the proinflammatory cytokines IL-12 and TNF-α. This study documents the previously unreported participation of the mannose receptor in the removal of apoptotic cells in the setting of tuberculosis (TB) infection. The results challenge the idea that apoptotic cell phagocytosis in TB has an immunogenic effect.