The effects of Trypanosome factors on Bovine Leukocyte function.

Abstract

African trypanosomes infect cattle and humans in tsetse fly-infested areas of sub-Saharan Africa, causing sleeping sickness in humans and nagana in livestock. To date, no vaccines are available to combat these economically important diseases. In order to develop safe and protective vaccines, the immunomodulatory role of parasite factors on immune function must be identified. The suppression of cellular responses is a characteristic feature of African trypanosomosis. In mice, certain aspects of immunosuppression are mediated by the generation of suppressive T-cells and by nitric oxide (NO) produced by gamma interferon (IFN-y)-activated macrophages. In order to ascertain which parasite factors induce the immunosuppression observed in bovine trypanosomosis, the effect of trypanosome factors on NO production by activated bovine peripheral blood mononuclear cells (PBMC) and monocytes as well as proliferative responses of stimulated PBMC, was measured. Cells were tested for their capacity to produce NO in response to activation with IFN-y and trypanosome factors and also for their proliferative capacity after stimulation with mitogens, trypanosome antigens and non-trypanosome antigens. Total mononuclear cell populations and adherent cells derived from uninfected N'Dama cattle and activated in vitro with IFN-y and trypanosome antigens, produced NO. Trypanosome antigens induced very low levels of NO production by both monocytes and PBMC. IFN-y acted synergistically with trypanosome antigens to induce higher levels of NO production. Both trypanosome and non-trypanosome antigens significantly decreased or almost completely blocked the proliferation of bovine PBMC to the recall antigen, foot and mouth disease vaccine (FMDV) antigen, but not to concanavalin A (Con A). These results suggest that immunosuppression observed in trypanosome-infected N'Dama cattle might be induced by specific trypanosome factors. However, these observations require further investigation