Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis

By D. Fitzner, M. Schnaars, D. van Rossum, G. Krishnamoorthy, P. Dibaj, Mostafa Bakhti, Tommy Regen, U. Hanisch, M. Simons. Journal of Cell Science, 2011

783 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/321681b57dc049b5abc2b31e43c647d4208c97e5

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Citations in the corpus

Exosome Uptake through Clathrin-mediated Endocytosis and Macropinocytosis and Mediating miR-21 Delivery* (2014, background): “Recently, phosphatidylserine on the exosome surface is reported to activate macropinocytosis in microglia (21).”
Routes and mechanisms of extracellular vesicle uptake (2014, background): “In phagocytic cells, inhibition of dynamin2 (85,86) prevented almost all EV internalization activity (24,27,28).”
Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake (2016, neutral): “…cells, caveolin-mediated endocytosis in epithelial cells, and cholesterol-and lipid raft-dependent endocytosis in tumor cells (Morelli et al. 2004; Barrès et al. 2010; Feng et al. 2010; Fitzner et al. 2011; Montecalvo et al. 2012; Frühbeis et al. 2013; Nanbo et al. 2013; Svensson et al. 2013).”
Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication (2013, background): “Microglia take up exosomes unspecifically by macropinocytosis [61], while internalization of oligodendroglial exosomes by neurons is mediated by selective clathrinand dynamin-dependent endocytosis.”
Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease (2019, background): “Exactly how these mechanisms apply to different vesicles and host cells may vary; however, the process of EV uptake appears to show some selectively (Blanchard et al., 2002; Fitzner et al., 2011; Horibe et al., 2018).”
MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles (2013, positive): “Although there is literature showing short-range diffusion of exosomes [70] and a short half-life time in serum due to possible circulation degradation or phagocytic clearance [71, 72], exosomes spread widely in the brain and exogenous exosomes may be used as a delivery vehicle [73, 74].”
Biological properties of extracellular vesicles and their physiological functions (2015, background): “Conversely, microglia mediated the immunologically silent clearance of EVs originating from other CNS cells (such as oligodendrocytes); at least under physiological conditions (98,592).”
Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. (2014, background): “…or phagocytosis in acidic compartments (Montecalvo et al. 2012) in DCs; dynamin-dependent but receptor-independent macropinocytosis in microglia (Fitzner et al. 2011); dynamin- and actin polymerization–dependent phagocytosis but also clathrin-dependent endocytosis in neurons (Fruhbeis et al.…”
SORTING IT OUT: REGULATION OF EXOSOME LOADING (2014, background): “Microglia take up exosomes nonspecifically by macropinocytosis [106], while internalization of oligodendroglial exosomes by neurons is mediated by selective clathrin- and dynamin-dependent endocytosis [107].”