Taylor K, Mertens B, Lutje V, Saya R
International Livestock Research Institute, PO Box 30709, Nairobi, Kenya.
Parasite Immunol. 1998 Sep;20(9):421-9. doi: 10.1046/j.1365-3024.1998.00165.x.
The mechanisms whereby trypanotolerant N'Dama cattle control infection with Trypanosoma congolense are unknown. Previous studies have suggested that the monocytes of N'Dama cattle are more highly activated during infection than those of trypanosusceptible Boran cattle. However, we have recently reported that the monocytes of Boran cattle have a reduced capacity to secrete nitric oxide during trypanosome infection. We therefore evaluated the production of nitric oxide by monocytes of trypanotolerant N'Dama cattle infected with T. congolense in response to interferon-gamma, bacterial lipopolysaccharide or trypanosome antigens. Interferon-gamma-induced nitric oxide production was decreased between days 25 and 76 of infection, while lipopolysaccharide-induced secretion of nitric oxide was increased at days 13 and again at day 76 post-infection. Trypanosome antigens did not elicit nitric oxide production. Analysis of interleukin-10 mRNA transcription in peripheral blood leucocytes revealed an increase at time points that coincided with decreased interferon-gamma-induced nitric oxide synthesis. In contrast, interferon-gamma mRNA expression was not changed during infection while tumour necrosis factor-alpha was slightly reduced at day 32 post-infection. Recombinant interleukin-10 suppressed interferon-gamma-induced nitric oxide and tumour necrosis factor-alpha secretion, but not lipopolysaccharide-induced nitric oxide secretion in cultures of peripheral blood mononuclear cells and monocytes of uninfected cattle. These results suggest that the nitric oxide response of monocytes to IFN-gamma but not lipopolysaccharide, is suppressed during infection. The kinetics of the upregulation of interleukin-10 and its biological activity indicate a possible association with the depression of nitric oxide production and control of tumour necrosis factor-alpha.
耐锥虫的恩达马牛控制刚果锥虫感染的机制尚不清楚。先前的研究表明，恩达马牛的单核细胞在感染期间比易感染锥虫的博拉牛的单核细胞具有更高的活性。然而，我们最近报道，博拉牛的单核细胞在锥虫感染期间分泌一氧化氮的能力降低。因此，我们评估了感染刚果锥虫的耐锥虫恩达马牛的单核细胞在受到干扰素-γ、细菌脂多糖或锥虫抗原刺激后一氧化氮的产生情况。在感染的第25天至76天之间，干扰素-γ诱导的一氧化氮产生减少，而脂多糖诱导的一氧化氮分泌在感染后第13天增加，并在第76天再次增加。锥虫抗原未引发一氧化氮的产生。对外周血白细胞中白细胞介素-10 mRNA转录的分析显示，在与干扰素-γ诱导的一氧化氮合成减少相吻合的时间点上有所增加。相比之下，感染期间干扰素-γ mRNA表达没有变化，而肿瘤坏死因子-α在感染后第32天略有降低。重组白细胞介素-10抑制了外周血单个核细胞和未感染牛单核细胞培养物中干扰素-γ诱导的一氧化氮和肿瘤坏死因子-α分泌，但不抑制脂多糖诱导的一氧化氮分泌。这些结果表明，感染期间单核细胞对IFN-γ而非脂多糖的一氧化氮反应受到抑制。白细胞介素-10上调的动力学及其生物学活性表明，它可能与一氧化氮产生的抑制以及肿瘤坏死因子-α的控制有关。
