CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation
Abstract Background The presence of foamy macrophages and microglia containing intracellular myelin remnants is a pathological hallmark of neurodegenerative disorders such as multiple sclerosis (MS). Despite the importance of myelin internalization in affecting both central nervous system repair and...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-01899-x |
| _version_ | 1819161988600692736 |
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| author | Elien Grajchen Elien Wouters Britt van de Haterd Mansour Haidar Kévin Hardonnière Tess Dierckx Jana Van Broeckhoven Celine Erens Sven Hendrix Saadia Kerdine-Römer Jerome J. A. Hendriks Jeroen F. J. Bogie |
| author_facet | Elien Grajchen Elien Wouters Britt van de Haterd Mansour Haidar Kévin Hardonnière Tess Dierckx Jana Van Broeckhoven Celine Erens Sven Hendrix Saadia Kerdine-Römer Jerome J. A. Hendriks Jeroen F. J. Bogie |
| author_sort | Elien Grajchen |
| collection | DOAJ |
| description | Abstract Background The presence of foamy macrophages and microglia containing intracellular myelin remnants is a pathological hallmark of neurodegenerative disorders such as multiple sclerosis (MS). Despite the importance of myelin internalization in affecting both central nervous system repair and neuroinflammation, the receptors involved in myelin clearance and their impact on the phagocyte phenotype and lesion progression remain to be clarified. Methods Flow cytometry, quantitative PCR, and immunohistochemistry were used to define the mRNA and protein abundance of CD36 in myelin-containing phagocytes. The impact of CD36 and nuclear factor erythroid 2–related factor 2 (NRF2) on the phagocytic and inflammatory features of macrophages and microglia was assessed using a pharmacological CD36 inhibitor (sulfo-N-succinimidyl oleate) and Nrf2 −/− bone marrow-derived macrophages. Finally, the experimental autoimmune encephalomyelitis (EAE) model was used to establish the impact of CD36 inhibition on neuroinflammation and myelin phagocytosis in vivo. Results Here, we show that the fatty acid translocase CD36 is required for the uptake of myelin debris by macrophages and microglia, and that myelin internalization increased CD36 expression through NRF2. Pharmacological inhibition of CD36 promoted the inflammatory properties of myelin-containing macrophages and microglia in vitro, which was paralleled by a reduced activity of the anti-inflammatory lipid-sensing liver X receptors and peroxisome proliferator-activated receptors. By using the EAE model, we provide evidence that CD36 is essential for myelin debris clearance in vivo. Importantly, CD36 inhibition markedly increased the neuroinflammatory burden and disease severity in the EAE model. Conclusion Altogether, we show for the first time that CD36 is crucial for clearing myelin debris and suppressing neuroinflammation in demyelinating disorders such as MS. |
| first_indexed | 2024-12-22T17:21:05Z |
| format | Article |
| id | doaj.art-48a6620689ed48feb27566498ac8333d |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-22T17:21:05Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-48a6620689ed48feb27566498ac8333d2022-12-21T18:18:49ZengBMCJournal of Neuroinflammation1742-20942020-07-0117111410.1186/s12974-020-01899-xCD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammationElien Grajchen0Elien Wouters1Britt van de Haterd2Mansour Haidar3Kévin Hardonnière4Tess Dierckx5Jana Van Broeckhoven6Celine Erens7Sven Hendrix8Saadia Kerdine-Römer9Jerome J. A. Hendriks10Jeroen F. J. Bogie11Department of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityInflammation, Microbiome and Immunosurveillance, INSERM UMR99, Université Paris-SaclayDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityInflammation, Microbiome and Immunosurveillance, INSERM UMR99, Université Paris-SaclayDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt UniversityAbstract Background The presence of foamy macrophages and microglia containing intracellular myelin remnants is a pathological hallmark of neurodegenerative disorders such as multiple sclerosis (MS). Despite the importance of myelin internalization in affecting both central nervous system repair and neuroinflammation, the receptors involved in myelin clearance and their impact on the phagocyte phenotype and lesion progression remain to be clarified. Methods Flow cytometry, quantitative PCR, and immunohistochemistry were used to define the mRNA and protein abundance of CD36 in myelin-containing phagocytes. The impact of CD36 and nuclear factor erythroid 2–related factor 2 (NRF2) on the phagocytic and inflammatory features of macrophages and microglia was assessed using a pharmacological CD36 inhibitor (sulfo-N-succinimidyl oleate) and Nrf2 −/− bone marrow-derived macrophages. Finally, the experimental autoimmune encephalomyelitis (EAE) model was used to establish the impact of CD36 inhibition on neuroinflammation and myelin phagocytosis in vivo. Results Here, we show that the fatty acid translocase CD36 is required for the uptake of myelin debris by macrophages and microglia, and that myelin internalization increased CD36 expression through NRF2. Pharmacological inhibition of CD36 promoted the inflammatory properties of myelin-containing macrophages and microglia in vitro, which was paralleled by a reduced activity of the anti-inflammatory lipid-sensing liver X receptors and peroxisome proliferator-activated receptors. By using the EAE model, we provide evidence that CD36 is essential for myelin debris clearance in vivo. Importantly, CD36 inhibition markedly increased the neuroinflammatory burden and disease severity in the EAE model. Conclusion Altogether, we show for the first time that CD36 is crucial for clearing myelin debris and suppressing neuroinflammation in demyelinating disorders such as MS.http://link.springer.com/article/10.1186/s12974-020-01899-xMacrophagesMicrogliaMyelinCD36NeuroinflammationFatty acid |
| spellingShingle | Elien Grajchen Elien Wouters Britt van de Haterd Mansour Haidar Kévin Hardonnière Tess Dierckx Jana Van Broeckhoven Celine Erens Sven Hendrix Saadia Kerdine-Römer Jerome J. A. Hendriks Jeroen F. J. Bogie CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation Journal of Neuroinflammation Macrophages Microglia Myelin CD36 Neuroinflammation Fatty acid |
| title | CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation |
| title_full | CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation |
| title_fullStr | CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation |
| title_full_unstemmed | CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation |
| title_short | CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation |
| title_sort | cd36 mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation |
| topic | Macrophages Microglia Myelin CD36 Neuroinflammation Fatty acid |
| url | http://link.springer.com/article/10.1186/s12974-020-01899-x |
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