Interferon‐γ and nitric oxide in combination with antibodies are key protective host immune factors during Trypanosoma congolense Tc13 Infections

The control of chronic Trypanosoma congolense trypanosomiasis was analyzed using several gene-deficient mouse strains. First, interferon (IFN)-gamma receptor ( IFN-gamma-R)-deficient mice were used to show that IFN-gamma-mediated immune activation is crucial for parasitemia control. Second, infections in major histocompatibility complex (MHC) class II-deficient mice indicate that this molecule is needed for initiation of IFN-gamma and subsequent tumor necrosis factor (TNF) production. Downstream of IFN-gamma-R signaling, inducible NO synthase (iNOS)-dependent trypanosome killing occurs, as is shown by the hypersusceptible phenotype of iNOS-deficient mice. Besides proinflammatory responses, B cells and, more specifically, immunoglobulin (Ig) G antibodies are crucial for parasite killing. Hence, parasitemia control is abolished in B cell-deficient mice, whereas IgM-deficient mice control the infection as efficiently as do wild-type mice. In addition, splenectomized mice that have a normal IgM response but an impaired IgG2a/3 response fail to control T. congolense infection. Collectively, these results suggest that host protective immunity against T. congolense is critically dependent on the combined action of the proinflammatory mediators/effectors IFN-gamma, TNF, and NO and antiparasite IgGs