CONCISE COMMUNICATION Human Macrophage Tumor Necrosis Factor (TNF)±a Production Induced by Trypanosoma brucei gambiense and the Role of TNF-a in Parasite Control

Trypanosoma brucei gambiense, a causative agent of sleeping sickness, induced a dose-de-pendent production of tumor necrosis factor (TNF)±a by human macrophages in vitro. TNF-a was also induced in the Mono Mac 6 cell line, which indicates a direct effect of parasite components on macrophages. Parasite-soluble factors were also potent inducers of TNF-a. The addition of anti±TNF-a to cocultures of macrophages and parasites increased the number of trypanosomes and their life span, whereas irrelevant antibodies had no effect. TNF-a may have a direct role (i.e., direct trypanolytic activity) and/or an indirect one, such as TNF-a±mediated induction of cytotoxic molecules. A direct dose-dependent lytic effect of TNF-a on puri®ed parasites was observed. This lytic effect was inhibited by anti±TNF-a. These data suggest that, as in experimental trypanosomiasis, TNF-a is involved in parasite growth control in human African trypanosomiasis. Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, the causative agents of human African trypano-somiasis (HAT), also called sleeping sickness, are tse-tse ¯y± transmitted protozoa that multiply extracellularly in the blood