Human macrophage tumor necrosis factor (TNF)-α production induced by Trypanosoma brucei gambiense and the role of TNF-α in parasite control

Human macrophage tumor necrosis factor (TNF)-α production induced by Trypanosoma brucei gambiense and the role of TNF-α in parasite control
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DOI:
10.1086/319257
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发表时间:
2001-03-15
影响因子:
6.4
通讯作者:
Vincendeau, P
Vincendeau, P
中科院分区:
医学2区
文献类型:
--
作者:
Daulouède, S;Bouteille, B;Vincendeau, P

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布氏冈比亚锥虫是一种昏睡病的病原体,在体外诱导人巨噬细胞产生肿瘤坏死因子-α,并呈剂量依赖关系。在Mono Mac 6细胞系中也能诱导出肿瘤坏死因子-α,这表明寄生虫成分对巨噬细胞有直接作用。寄生虫可溶性因子也是肿瘤坏死因子-α的有效诱导物。在巨噬细胞和寄生虫的共培养中加入抗肿瘤坏死因子-α可增加锥虫的数量和寿命,而无关抗体则不起作用。肿瘤坏死因子-α可能具有直接作用(即直接的胰酶溶解活性)和/或间接作用,如肿瘤坏死因子-α介导的细胞毒分子的诱导。观察到肿瘤坏死因子-α对纯化寄生虫的直接裂解作用,呈剂量依赖关系。这种溶解作用可被抗肿瘤坏死因子-α抗体所抑制。这些数据表明,与实验性锥虫病一样,肿瘤坏死因子-α参与了人类非洲锥虫病的寄生虫生长控制。
Trypanosoma brucei gambiense, a causative agent of sleeping sickness, induced a dose-dependent production of tumor necrosis factor (TNF)-alpha by human macrophages in vitro. TNF-alpha was also induced in the Mono Mac 6 cell line, which indicates a direct effect of parasite components on macrophages. Parasite-soluble factors were also potent inducers of TNF-alpha. The addition of anti-TNF-alpha to cocultures of macrophages and parasites increased the number of trypanosomes and their life span, whereas irrelevant antibodies had no effect. TNF-alpha may have a direct role (i.e., direct trypanolytic activity) and/or an indirect one, such as TNF alpha -mediated induction of cytotoxic molecules. A direct dose-dependent lytic effect of TNF-alpha on purified parasites was observed. This lytic effect was inhibited by anti-TNF-alpha. These data suggest that, as in experimental trypanosomiasis, TNF-alpha is involved in parasite growth control in human African trypanosomiasis.