Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis.
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.
Max-Planck Institute for Experimental Medicine, Hermann-Rein-Str., D-37075 Göttingen, Germany.
Dirk
D
Fitzner
Mareike
M
Schnaars
Denise
D
van Rossum
Gurumoorthy
G
Krishnamoorthy
Payam
P
Dibaj
Mostafa
M
Bakhti
Tommy
T
Regen
Uwe-Karsten
UK
Hanisch
Mikael
M
Simons
D000818:Animals; D001692:Biological Transport; D055354:Exosomes / Q000378:metabolism*; D005802:Genes, MHC Class II; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism*; D010873:Pinocytosis / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism