Bogdan C, Moll H, Solbach W, Röllinghoff M
Institute of Clinical Microbiology, University of Erlangen, FRG.
Eur J Immunol. 1990 May;20(5):1131-5. doi: 10.1002/eji.1830200528.
We have previously shown that during an infection with Leishmania major, susceptible BALB/c mice, as opposed to mice of a resistant strain (C57BL/6), are primed by lipopolysaccharide for the production of high levels of tumor necrosis factor-alpha (TNF-alpha) which is known to be a potent macrophage (M phi) stimulator in other parasitic diseases. In the present study we investigated whether TNF-alpha activates M phi for killing of L. major parasites. In the absence of interferon-gamma (IFN-gamma) or lipopolysaccharide, TNF-alpha (0.025-25,000 U/ml) failed to activate peritoneal exudate M phi from BALB/c mice for killing of L. major amastigotes. In the presence of suboptimal doses of IFN-gamma (5 or 10 U/ml), however, TNF-alpha mediated a rapid elimination of intracellular parasites, which was highly significant compared to IFN-gamma alone. The combination of TNF with interleukin 4, in contrast, was inactive in this respect and allowed survival of intracellular parasites. From these data we conclude that the presence of IFN-gamma is crucial for TNF-alpha-mediated killing of L. major parasites by M phi. Disease progression in susceptible mice therefore seems to be a consequence of a deficiency of IFN-gamma and a predominance of interleukin 4 rather than the result of an excess amount of TNF-alpha.
我们之前已经表明，在感染硕大利什曼原虫期间，与抗性品系（C57BL/6）小鼠不同，易感的BALB/c小鼠会被脂多糖致敏，从而产生高水平的肿瘤坏死因子-α（TNF-α），已知该因子在其他寄生虫病中是一种有效的巨噬细胞刺激剂。在本研究中，我们调查了TNF-α是否激活巨噬细胞以杀死硕大利什曼原虫。在没有干扰素-γ（IFN-γ）或脂多糖的情况下，TNF-α（0.025 - 25,000 U/ml）未能激活BALB/c小鼠的腹腔渗出巨噬细胞以杀死硕大利什曼原虫无鞭毛体。然而，在次优剂量的IFN-γ（5或10 U/ml）存在的情况下，TNF-α介导了细胞内寄生虫的快速清除，与单独使用IFN-γ相比，这具有高度显著性。相比之下，TNF与白细胞介素4的组合在这方面没有活性，并且允许细胞内寄生虫存活。从这些数据我们得出结论，IFN-γ的存在对于TNF-α介导的巨噬细胞杀死硕大利什曼原虫至关重要。因此，易感小鼠的疾病进展似乎是IFN-γ缺乏和白细胞介素4占优势的结果，而不是TNF-α过量的结果。
