Tumor necrosis factor alpha is a key mediator in the regulation of experimental Trypanosoma brucei infections

Abstract

In order to evaluate during experimental Trypanosoma brucei infections the potential role of tumor necrosis factor alpha (TNF-α) in the host- parasite interrelationship, C57BL/6 TNF-α knockout mice (TNF-α(-/-)) as well as C57BL/6 wild-type mice were infected with pleomorphic T. brucei AnTat 1.1 E parasites. In the TNF-α(-/-) mice, the peak levels of parasitemia were strongly increased compared to the peak levels recorded in wild-type mice. The increased parasite burden did not reflect differences in clearance efficacy or in production of T. brucei-specific immunoglobulin M (IgM) and IgG antibodies. Trypanosome-mediated immunopathological features, such as lymph node-associated immunosuppression and lipopolysaccharide hypersensitivity, were found to be greatly reduced in infected TNF-α(-/-) mice. These results demonstrate that, during trypanosome infections, TNF-α is a key mediator involved in both parasitemia control and infection- associated pathology.