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Alternative versus classical macrophage activation during experimental African trypanosomosis
P D Baetselier1, B Namangala, W Noël
1Department of Immunology, Parasitology and Ultrastructure, Flemish Interuniversity Institute for Biotechnology, Free University Brussels (VUB), Paardenstraat 65, B-1640 St-Genesius-Rode, Belgium.
International Journal for Parasitology
|May 4, 2001
Summary
Understanding African trypanosome infection requires a balanced immune response. A type I cytokine environment with classical macrophage activation early on, followed by a type II cytokine shift, promotes chronic infection and survival.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- African trypanosomes cause fatal sleeping sickness and nagana.
- Immune responses, particularly cytokine profiles and macrophage activation, are key to resistance or susceptibility.
- The role of phospholipase C (PLC) null mutant (PLC(-/-)) versus wild-type (WT) Trypanosoma brucei infections in shaping these responses is unclear.
Purpose of the Study:
- To investigate the immune response, focusing on cytokine profiles and macrophage activation, in mice infected with T. brucei PLC(-/-) or WT parasites.
- To compare the immune mechanisms underlying resistance and susceptibility to African trypanosome infections.
Main Methods:
- Infection of mice with T. brucei PLC(-/-) and WT parasites.
- Analysis of cytokine production (Type I and Type II) at different infection stages.
- Assessment of macrophage phenotype (classical vs. alternative activation) and function.
Main Results:
- T. brucei PLC(-/-) infection led to chronic disease with early Type I and late Type II cytokine production, promoting alternative macrophage activation.
- WT T. brucei infection resulted in rapid death, with a sustained Type I cytokine response and classical macrophage activation.
- Susceptibility to Trypanosoma congolense was associated with higher early Type II cytokines, while resistance involved controlling parasitemia.
Conclusions:
- Survival to African trypanosome infection necessitates an early Type I cytokine environment and classical macrophage activation to control initial parasite load.
- A subsequent switch to a Type II cytokine environment and alternative macrophage activation is crucial for disease progression into a chronic, non-lethal phase.
- Sequential macrophage activation plays a significant role in resistance to T. brucei infections.