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Analysis of the Impact of CD200 on Phagocytosis

Molecular Neurobiology volume 54, pages 5730–5739 (2017)Cite this article

Abstract

One factor that impacts on microglial activation is the interaction between the ubiquitously expressed CD200 and CD200R, which is expressed only on microglia in the brain. Decreased signalling through CD200R, when CD200 expression is reduced, results in microglial activation and may, at least in part, explain the increased cell activity that is observed with age, in models of Alzheimer’s and Parkinson’s disease as well as in the human diseases. There is evidence of increased microglial activation in CD200-deficient mice, and isolated microglia prepared from these mice are more reactive to inflammatory stimuli like Toll-like receptor 2 and 4 agonists, and interferon-γ. Here, we examined the impact of CD200 deficiency on amyloid-β (Aβ)-induced changes in microglia and report, perhaps unexpectedly, that the effect of Aβ was attenuated in microglia prepared from CD200-deficient mice. The evidence indicates that this is a consequence of increased phagocytosis, associated with increased lysosomal activity in CD200-deficient microglia. The data suggest that mTOR-related signalling is decreased in these cells and that inhibiting mTOR by rapamycin increases phagocytosis. Thus, while the findings to date have emphasized the anti-inflammatory effects of CD200-CD200R interaction, the present evidence indicates a previously unreported impact on lysosomal function.

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Acknowledgments

The authors gratefully acknowledge funding from the Science Foundation Ireland to MAL (07/IN.1/B949 and 11/PI/1014). AL was supported by a post-doctoral fellowship from the Health Research Board Ireland.

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Authors and Affiliations

  1. Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland

    Anthony Lyons, Aedín M. Minogue, Raasay S. Jones, Orla Fitzpatrick, Janis Noonan, Veronica A. Campbell & Marina A. Lynch

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  1. Anthony Lyons
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  2. Aedín M. Minogue
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  3. Raasay S. Jones
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  5. Janis Noonan
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  7. Marina A. Lynch
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Correspondence to Marina A. Lynch.

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Animal experimentation was performed under a licence granted by the Minister for Health and Children (Ireland) under the Cruelty to Animals Act 1876 and the European Community Directive, 86/609/EEC, and in accordance with local ethical guidelines.

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Lyons, A., Minogue, A.M., Jones, R.S. et al. Analysis of the Impact of CD200 on Phagocytosis. Mol Neurobiol 54, 5730–5739 (2017). https://doi.org/10.1007/s12035-016-0223-6

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  • DOI: https://doi.org/10.1007/s12035-016-0223-6

Keywords

  • Microglial activation
  • CD200
  • Amyloid-β
  • Phagocytosis
  • Lysosome