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Evaluation of Extracellular Vesicle Function During Malaria Infection
Published on: February 14, 2018
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Human Microglia Respond to Malaria-Induced Extracellular Vesicles
Smart Ikechukwu Mbagwu1,2, Nils Lannes1, Michael Walch1
1Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland.
Pathogens (Basel, Switzerland)
|December 28, 2019
Summary
Malaria-infected red blood cell extracellular vesicles (MiREVs) enter brain microglia, increasing the inflammatory cytokine TNFα and decreasing IL-10. This interaction may worsen neuroinflammation in cerebral malaria.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Infectious Diseases
Background:
- Microglia are key brain immune cells, activated in severe malaria, potentially driving neuroinflammation.
- Malaria-infected red blood cell extracellular vesicles (MiREVs) mediate cell communication and immune regulation.
- Blood-brain barrier disruption in cerebral malaria allows peripheral substances like MiREVs to enter the brain and affect microglia.
Purpose of the Study:
- To investigate the uptake of MiREVs by human microglia.
- To determine the cytokine response of microglia upon MiREVs exposure.
- To explore the role of microglia-extracellular vesicle interaction in malaria infection.
Main Methods:
- Generated human monocyte-derived microglia (MoMi) from healthy donor buffy coats.
- Isolated and purified MiREVs from Plasmodium falciparum cultures, labeling them with a green fluorescent dye.
- Utilized confocal microscopy to observe MiREVs internalization by MoMi and rt-qPCR to analyze cytokine gene expression.
Main Results:
- Confirmed internalization and perinuclear accumulation of MiREVs within microglia.
- Observed increased gene expression of the pro-inflammatory cytokine TNFα in MiREVs-treated microglia.
- Found reduced gene expression of the immunosuppressive cytokine IL-10 following MiREVs exposure.
Conclusions:
- MiREVs are internalized by human microglia.
- MiREVs alter microglia cytokine profiles, promoting inflammation.
- Microglia-MiREVs interaction may contribute to neuroinflammation in cerebral malaria.
