Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis

Author:

Fitzner Dirk12,Schnaars Mareike1,van Rossum Denise3,Krishnamoorthy Gurumoorthy4,Dibaj Payam2,Bakhti Mostafa1,Regen Tommy3,Hanisch Uwe-Karsten3,Simons Mikael12

Affiliation:

1. Max-Planck Institute for Experimental Medicine, Hermann-Rein-Str., D-37075 Göttingen, Germany

2. Department of Neurology, University of Göttingen, D-37075 Göttingen, Germany

3. Institute of Neuropathology, University of Göttingen, D-37075 Göttingen, Germany

4. Department of Neuroimmunology, Max-Planck Institute of Neurobiology, D-82152 Martinsried, 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.

Publisher

The Company of Biologists

Subject

Cell Biology

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