Trypanosoma congolense infection of trypanotolerant N'Dama (Bos taurus) cattle is associated with decreased secretion of nitric oxide by interferon-gamma-activated monocytes and increased transcription of interleukin-10

The mechanisms whereby trypanotolerant N'Dama cattle control infection with Trypanosoma congolense are unknown. Previous studies have suggested that t he monocytes of N'Dama cattle are more highly activated during infection th an those of trypanosusceptible Boran cattle. However, we have recently repo rted that the monocytes of Boran cattle have a reduced capacity to secrete nitric oxide during trypanosome infection. We therefore evaluated the produ ction of nitric oxide by monocytes of trypanotolerant N'Dama cattle infecte d with T. congolense in response to interferon-gamma, bacterial lipopolysac charide or trypanosome antigens. Interferon-gamma-induced nitric oxide prod uction was decreased between days 25 and 76 of infection, while lipopolysac charide-induced secretion of nitric oxide was increased at days 13 and agai n at day 76 post-infection. Trypanosome antigens did not elicit nitric oxid e production. Analysis of interleukin-10 mRNA transcription in peripheral b lood leucocytes revealed an increase at time points that coincided with dec reased interferon-gamma-induced nitric oxide synthesis. In contrast interfe ron-gamma mRNA expression was not changed during infection while tumour nec rosis factor-alpha was slightly reduced at day 32 post-infection. Recombina nt interleukin-10 suppressed interferon-gamma-induced nitric oxide and tumo ur necrosis factor-alpha secretion, bur not lipopolysaccharide-induced nitr ic oxide secretion in cultures of peripheral blood mononuclear cells and mo nocytes of uninfected cattle. These results suggest that the nitric oxide r esponse of monocytes to IFN-gamma but not lipopolysaccharide, is suppressed during infection The kinetics of the upregulation of interleukin-10 anti i ts biological activity indicate a possible association with the depression of nitric oxide production and control of tumour necrosis factor-alpha.