[Defense mechanisms in trypanosomiasis]

Quantitative and functional alterations in macrophages are observed in trypanosomiasis. Two molecules from macrophages exert potent anti-microbial effect: Nitric Oxide (NO) and Tumor Necrosis Factor-alpha (TNF-alpha). The role of NO in trypanosomiasis is investigated at first on a murine parasite. Trypanosoma musculi, at first and then on Trypanosoma brucei gambiense and T. brucei brucei. Macrophages from T. musculi-infected mice synthesize NO and their trypanostatic activity is correlated with NO production. In vitro activation of macrophage NO synthase by IFN-gamma induces a trypanostatic activity and TNF-alpha is involved in NO synthase induction. High serum levels of TNF-alpha are correlated with disease severity in human African trypanosomiasis. TNF-alpha is increased in supernatants of leucocyte and trypanosome cocultures. TNF-alpha exerts a strong anti-trypanosomal effect. Messengers RNA of TNF-alpha are detected in monocytes after 8 hours of coculture with trypanosomes. Macrophage effector molecules participate with other immune effector mechanisms in resistance of host to trypanosomes.