Mononuclear-macrophages but not neutrophils act as major infiltrating anti-leptospiral phagocytes during leptospirosis.
Mononuclear-macrophages but not neutrophils act as major infiltrating anti-leptospiral phagocytes during leptospirosis.
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在钩端螺旋体病期间，单核巨噬细胞而非中性粒细胞充当主要的浸润性抗钩端螺旋体吞噬细胞
DOI：
10.1371/journal.pone.0181014
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Chen X;Li SJ;Ojcius DM;Sun AH;Hu WL;Lin X;Yan J
鉴定钩端螺旋体病过程中主要渗入的吞噬细胞，研究宿主灭除问号钩端螺旋体的作用机制。用免疫组织化学方法检测钩端螺旋体感染的C3H/HEJ小鼠体内的主要吞噬细胞。应用基因芯片和免疫组织化学方法检测钩端螺旋体感染小鼠和钩端螺旋体病人体内趋化因子和血管内皮细胞黏附分子(VECAM)的表达。用共聚焦显微镜和荧光分光光度法检测钩端螺旋体对人或小鼠巨噬细胞和中性粒细胞的吞噬和杀伤能力以及细胞内ROS、NO和[Ca~(2+)]i在钩端螺旋体杀伤过程中的作用。感染小鼠肺、肝、肾的吞噬细胞主要是外周血单核巨噬细胞，而不是中性粒细胞。在感染小鼠和患者的样本中，巨噬细胞特异性趋化因子和VECAM水平显著增加，但中性粒细胞特异性趋化因子和VECAM水平并不显著。所有测试的巨噬细胞都比中性粒细胞具有更高的吞噬和杀灭钩端螺旋体的能力。巨噬细胞内较高的ROS、NO水平和[Ca~(2+)]i参与了钩端螺旋体的杀灭。人巨噬细胞表现出比小鼠巨噬细胞更多的吞噬酶体形成和更强的钩端螺旋体杀灭能力。在钩端螺旋体病中，单核巨噬细胞而不是中性粒细胞是主要的浸润性和抗钩端螺旋体吞噬细胞。较低水平的吞噬小体-溶酶体融合可能是人巨噬细胞杀灭钩端螺旋体能力较低的原因。
To identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate Leptospira interrogans. Major infiltrating phagocytes in Leptospira-infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and leptospirosis patients were detected by microarray and immunohistochemistry. Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira-killing process were evaluated by confocal microscopy and spectrofluorimetry. Peripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver and kidneys of infected mice. Levels of macrophage- but not neutrophil-specific chemokines and VECAMs were significantly increased in the samples from infected mice and patients. All macrophages tested had a higher ability than neutrophils to phagocytose and kill leptospires. Higher ROS and NO levels and [Ca2+]i in the macrophages were involved in killing leptospires. Human macrophages displayed more phagolysosome formation and a stronger leptospire-killing ability to than mouse macrophages. Mononuclear-macrophages but not neutrophils represent the main infiltrating and anti-leptospiral phagocytes during leptospirosis. A lower level of phagosome-lysosome fusion may be responsible for the lower Leptospira-killing ability of human macrophages.
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