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Human microglia respond to malaria‐induced extracellular vesicles
Author(s) -
Mbagwu Smart,
Lannes Nils,
Walch Micheal,
Filgueira Luis,
Mantel Pierre-Yves
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02528
Subject(s) - microglia , neuroinflammation , cerebral malaria , immune system , extracellular , biology , microbiology and biotechnology , plasmodium falciparum , immunology , cytokine , differential centrifugation , microvesicles , cd63 , malaria , inflammation , biochemistry , microrna , gene
Background and Objective Microglia are the chief immune cells of the brain and have been reported to be activated in severe malaria. Their activation may drive towards neuroinflammation in cerebral malaria. Malaria‐infected red blood cell derived‐extracellular vesicles (MiREVs) are produced during the blood stage of malaria infection. They mediate intercellular communication and immune regulation among other functions. During cerebral malaria, the breakdown of the blood‐brain barrier can promote the migration of substances such as MiREVs from the periphery into the brain targeting cells such as microglia. Microglia and extracellular vesicles interactions in different pathological conditions have been reported to induce neuroinflammation. Unlike in astrocytes, microglia‐extracellular vesicle interaction has not yet been described in malaria infection. Therefore, in this study, we aimed at investigating the uptake of malaria‐infected red blood cell derived‐extracellular vesicles (MiREVs) by human microglia cells and their cytokine response. Method Human blood monocyte‐derived microglia were generated from buffy coats of anonymous healthy donors using Ficoll‐Paque density gradient centrifugation. The malaria infected red blood cell derived‐EVs (MiREVs) were isolated from the Plasmodium falciparum cultures. They were purified by ultracentrifugation and labelled with PKH67 green fluorescent dye. The internalization of MiREVs by MoMi was observed after 4hours of co‐incubation on coverslips placed in a 24‐well plate at 37°C using confocal microscopy. Cytokine‐gene expression was investigated using rt‐qPCR following the stimulation of the MoMi cells with supernatants from the parasite cultures at 2,4 and 24h respectively. Results and Conclusion MiREVs were internalized by the microglia and accumulated in the perinuclear region. MiREVs‐treated cells increased gene expression of the inflammatory cytokine TNFα and reduced gene expression of the immune suppressive IL‐10. Overall, the results indicate that MiREVs may act on microglia which would contribute to enhanced inflammation in cerebral malaria.