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Oxygen-dependent leishmanicidal activity of stimulated macrophages
R Chakraborty1, S Mukherjee, M K Basu
1Biomembrane Division, Indian Institute of Chemical Biology, Calcutta, India.
Abstract:
Peritoneal macrophages pretreated with different stimulants were analysed and compared with their respective controls for their ability to kill intracellular pathogenic L. donovani, (MHOM/IN/1983/AG83) an isolate from Indian subcontinent. Stimulation of macrophages by zymosan showed a higher microbicidal activity as compared to that by PMA. A correlation between microbicidal activity of the macrophages and the parameters related to respiratory burst activity such as liberation of O2-, production of H2O2 and consumption of O2 was sought. All the parameters showed a decrease in case of infected macrophages in comparison to those of the non-infected ones. Thus, it is possible that the impairment of macrophage activation by intracellular Leishmania contributes to their survival in the toxic environment of the host.
Insights
Macrophages stimulated by zymosan exhibited enhanced killing of Leishmania donovani compared to PMA. Intracellular Leishmania parasites impair macrophage respiratory burst activity, aiding their survival.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Peritoneal macrophages are crucial immune cells for combating intracellular pathogens.
- Leishmania donovani is an intracellular parasite responsible for leishmaniasis.
- Macrophage activation and respiratory burst are key mechanisms for pathogen clearance.
Purpose of the Study:
- To compare the microbicidal activity of peritoneal macrophages stimulated with different agents against Leishmania donovani.
- To investigate the correlation between macrophage microbicidal activity and respiratory burst parameters.
- To understand how Leishmania donovani infection affects macrophage activation.
Main Methods:
- Peritoneal macrophages were isolated and pretreated with stimulants like zymosan and phorbol myristate acetate (PMA).
- Macrophage microbicidal activity against intracellular L. donovani (MHOM/IN/1983/AG83) was assessed.
- Respiratory burst activity was measured by quantifying superoxide anion (O2-) liberation, hydrogen peroxide (H2O2) production, and oxygen (O2) consumption.
Main Results:
- Zymosan stimulation resulted in higher microbicidal activity compared to PMA stimulation.
- A decrease in O2- liberation, H2O2 production, and O2 consumption was observed in infected macrophages versus non-infected controls.
- Impaired respiratory burst activity correlated with reduced microbicidal capacity.
Conclusions:
- Leishmania donovani infection impairs macrophage activation and respiratory burst.
- This impairment contributes to the survival of Leishmania parasites within the host macrophages.
- Targeting macrophage activation pathways could be a strategy for leishmaniasis treatment.