Tumor necrosis factor receptor 2 plays a minor role for mycobacterial immunity
Tumor necrosis factor receptor 2 plays a minor role for mycobacterial immunity
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DOI：
10.1159/000028116
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发表时间：
2000-03-01
期刊：
影响因子：
5
通讯作者：
Ryffel, B
中科院分区：
文献类型：
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作者：
Jacobs, M;Brown, N;Ryffel, B
肿瘤坏死因子（TNF）通过TNF受体1（TNF-R1）信号传导是宿主抵抗分枝杆菌感染所必需的。TNF-R2在抗分枝杆菌免疫中的作用尚不清楚。因此，我们比较了用牛分枝杆菌BCG（10（7）CFU，i. v.）感染的TNF-R1和TNF-R2敲除（KO）小鼠。虽然TNF-R1缺陷型小鼠的细菌负荷显著增加，并且小鼠在4至5周之间死于感染，但TNF-R2 KO小鼠较不敏感，并且10只小鼠中仅3只在12周内死亡。野生型（WT）小鼠对BCG感染具有抗性。无法清除TNF-R1 KO小鼠的感染与对纯化蛋白衍生物的迟发型超敏反应（DTH）降低、肉芽肿形成严重受损、巨噬细胞募集和活化减少以及粘附分子表达减少有关。相比之下，TNF-R2 KO小鼠与WT小鼠一样发展正常的DTH反应和成熟的分枝杆菌肉芽肿。因此，抗分枝杆菌免疫在很大程度上依赖于通过TNF-R1的TNF信号传导，而TNF-R2的活化起次要作用。版权所有（C）2000 S. Karger AG，巴塞尔。
Tumor necrosis factor (TNF) signalling via the TNF receptor 1 (TNF-R1) is required for host resistance to mycobacterial infection. The role of TNF-R2 in anti-mycobacterial immunity is not known. Therefore, we compa red TNF-R1 and TNF-R2 knockout (KO) mice infected with Mycobacterium bovis BCG (10(7) CFU, i.v.). While the bacterial burden of TN F-R l-deficient mice was significantly increased and the mice succumbed to infection between 4 and 5 weeks, TNF-R2 KO mice were less sensitive, and only 3 of 10 mice died within 12 weeks. Wild-type (WT) mice were resistant to BCG infection. The inability to clear the infection of TNF-R1 KO mice was associated with a reduced delayed-type hypersensitivity (DTH) response to purified protein derivative and severe impairment in forming granulomas with reduced macrophage recruitment and activation, and diminished expression of adhesion molecules. By contrast, TNF-R2 KO mice developed normal DTH response and mature mycobactericidal granulomas as the WT mice. Therefore, anti-mycobacterial immunity is largely dependent on TNF signalling via the TNF-R1, while activation of TNF-R2 plays a minor role. Copyright (C) 2000 S. Karger AG, Basel.