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Updated: Jun 5, 2026
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis
Dirk Fitzner1, Mareike Schnaars, Denise van Rossum
1Max-Planck Institute for Experimental Medicine, Hermann-Rein-Str., D-37075 Göttingen, Germany.
Abstract:
The transfer of antigens from oligodendrocytes to immune cells has been implicated in the pathogenesis of autoimmune diseases. Here, we show that oligodendrocytes secrete small membrane vesicles called exosomes, which are specifically and efficiently taken up by microglia both in vitro and in vivo. Internalisation of exosomes occurs by a macropinocytotic mechanism without inducing a concomitant inflammatory response. After stimulation of microglia with interferon-γ, we observe an upregulation of MHC class II in a subpopulation of microglia. However, exosomes are preferentially internalised in microglia that do not seem to have antigen-presenting capacity. We propose that the constitutive macropinocytotic clearance of exosomes by a subset of microglia represents an important mechanism through which microglia participate in the degradation of oligodendroglial membrane in an immunologically 'silent' manner. By designating the capacity for macropinocytosis and antigen presentation to distinct cells, degradation and immune function might be assigned to different subtypes of microglia.
Insights
Oligodendrocytes release exosomes, which microglia engulf via macropinocytosis. This process is immunologically silent, suggesting distinct microglia subtypes handle degradation and immune response in autoimmune diseases.
Area of Science:
- Neuroimmunology
- Cell Biology
- Autoimmune Disease Pathogenesis
Background:
- Oligodendrocyte-immune cell interactions are crucial in autoimmune diseases.
- Antigen transfer from oligodendrocytes to immune cells is a suspected mechanism.
Purpose of the Study:
- To investigate the mechanism of exosome uptake by microglia.
- To determine the immunological consequences of this interaction.
Main Methods:
- In vitro and in vivo studies of oligodendrocyte-derived exosome uptake by microglia.
- Analysis of microglial response to exosome internalization, including inflammatory markers and MHC class II expression.
- Investigation of the macropinocytotic pathway.
Main Results:
- Oligodendrocytes secrete exosomes that are efficiently internalized by microglia through macropinocytosis.
- Exosome uptake does not induce an immediate inflammatory response.
- Microglia with antigen-presenting capacity showed upregulated MHC class II after interferon-γ stimulation, but exosomes were preferentially taken up by microglia lacking this capacity.
- This suggests an immunologically 'silent' degradation pathway.
Conclusions:
- Microglia constitutively clear oligodendrocyte exosomes via macropinocytosis in an immunologically silent manner.
- This mechanism facilitates the degradation of oligodendroglial membrane.
- Distinct microglia subtypes may be specialized for degradation versus immune surveillance, impacting autoimmune disease pathogenesis.
