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Macrophage activation by Tetrahymena pyriformis. I. Active subcellular fractions of Tetrahymena
Abstract:
Experiments were carried out to determine what subcellular fractions of Tetrahymena pyriformis could, after inoculation into mice, activate macrophages to kill Toxoplasma gondii in vitro. Peritoneal macrophages from mice inoculated intraperitoneally with cilia, pellicles, mitochondria, and microsomes exhibited strong toxoplasmacidal activity and had an enhanced capacity to release hydrogen peroxide (H2O2) by stimulation of a membrane-active agent as compared with resident macrophages. In contrast, macrophages from mice inoculated with macronuclei and postmicrosomal supernatant showed no toxoplasmacidal activity and a low level of H2O2 release. Similar dose response was observed on the active subcellular fractions with regard to the degree of macrophage activation. Treatment of the active subcellular fractions with heating and trypsin markedly reduced their activity.
Insights
Certain Tetrahymena pyriformis subcellular fractions, like cilia and mitochondria, effectively activate mouse macrophages to kill Toxoplasma gondii. This activation involves enhanced hydrogen peroxide (H2O2) release, crucial for parasite clearance.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Toxoplasma gondii is an opportunistic parasite causing significant human disease.
- Macrophage activation is key to controlling parasitic infections.
- Identifying specific parasite components that induce macrophage activation is crucial for developing novel therapies.
Purpose of the Study:
- To identify which subcellular fractions of Tetrahymena pyriformis can activate mouse macrophages.
- To investigate the mechanism of macrophage activation, specifically focusing on hydrogen peroxide (H2O2) production.
- To determine the role of specific cellular components in inducing toxoplasmacidal activity.
Main Methods:
- Mice were inoculated intraperitoneally with various subcellular fractions of Tetrahymena pyriformis.
- Peritoneal macrophages were isolated and assessed for their ability to kill Toxoplasma gondii in vitro.
- Hydrogen peroxide (H2O2) release from stimulated macrophages was measured.
- The effect of heat and trypsin treatment on the activity of subcellular fractions was evaluated.
Main Results:
- Cilia, pellicles, mitochondria, and microsomes from Tetrahymena pyriformis induced significant toxoplasmacidal activity in mouse macrophages.
- Macrophages from mice inoculated with these fractions showed enhanced H2O2 release upon stimulation.
- Macronuclei and postmicrosomal supernatant fractions did not induce significant toxoplasmacidal activity or H2O2 release.
- The activity of the effective fractions was reduced by heat and trypsin treatment, suggesting a protein component.
Conclusions:
- Specific subcellular components of Tetrahymena pyriformis, particularly membrane-associated fractions, can potently activate macrophages.
- This activation is linked to an enhanced capacity for H2O2 production, contributing to parasite killing.
- These findings highlight potential targets for immunomodulatory strategies against Toxoplasma gondii infections.