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Trypanosoma brucei: susceptibility to hydrogen peroxide and related products of activated macrophages
1Cell Biology Research Group, Brunel University, Uxbridge, England, United Kingdom.
Abstract:
The susceptibility of procyclic, trypsinized, or bloodstream forms of Trypanosoma brucei to lysis by hydrogen peroxide and by activated mouse macrophages was investigated in vitro using the release of biosynthetically labeled proteins as an assay. Uncoated parasites were more resistant than coated bloodstream forms in both cases. Macrophage trypanolysis upon triggering with phorbol myristate acetate occurred extracellularly and seemed to depend on the release of hydrogen peroxide, as it was prevented by catalase. However, when presented trypanosomes in presence of fresh immune serum which was itself lytic, macrophages did not show any additional lytic effect, and phagocytosis was related to already damaged parasites.
Insights
Trypanosoma brucei parasites, particularly uncoated forms, show resistance to hydrogen peroxide and macrophage lysis. Macrophage activity against these parasites relies on hydrogen peroxide release and is less effective on already damaged trypanosomes.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Trypanosoma brucei is a protozoan parasite that causes African trypanosomiasis.
- Understanding parasite susceptibility to host immune mechanisms is crucial for developing treatments.
Purpose of the Study:
- To investigate the in vitro susceptibility of different Trypanosoma brucei forms to hydrogen peroxide and activated mouse macrophages.
- To elucidate the mechanisms of macrophage-mediated trypanolysis.
Main Methods:
- Investigated lysis of procyclic, trypsinized, and bloodstream forms of Trypanosoma brucei.
- Used release of biosynthetically labeled proteins as an assay for parasite lysis.
- Activated mouse macrophages with phorbol myristate acetate and assessed lysis with and without catalase or immune serum.
Main Results:
- Uncoated Trypanosoma brucei forms were more resistant to lysis by hydrogen peroxide and macrophages compared to coated forms.
- Macrophage-mediated trypanolysis was extracellular and dependent on hydrogen peroxide release, as evidenced by inhibition with catalase.
- Macrophages showed no additional lytic effect when trypanosomes were opsonized with lytic immune serum; phagocytosis occurred primarily with already damaged parasites.
Conclusions:
- Different life cycle stages and surface properties of Trypanosoma brucei influence their susceptibility to host innate immune components.
- Hydrogen peroxide is a key mediator of macrophage-induced lysis of Trypanosoma brucei.
- Macrophage phagocytosis is a secondary mechanism, often acting on parasites already compromised by other immune factors.