African trypanosome infections in mice that lack the interferon‐γ receptor gene: nitric oxide‐dependent and ‐independent suppression of T‐cell proliferative responses and the development of anaemia

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Abstract
Infection of mice with African trypanosomes leads to a severe immunosuppression, mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo cell transfer, it has been shown that nitric oxide (NO) is a potent effector product of these cells and causes both lymphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-γ-receptor gene, which were unable to respond with macrophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early stages of infection. The data indicate that, in the mouse, NO is a significant mediator of immunosuppression only in early infection. Beyond day 10 of infection, NO-independent mechanisms are of primary significance and the control of parasitaemia and T-cell responsiveness are not directly related.
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