Brain-to-gut trafficking of alpha-synuclein by CD11c+ cells in a mouse model of Parkinson’s disease

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作者：
Rhonda L. McFleder
Anastasiia Makhotkina
Janos Groh
Ursula Keber
Fabian Imdahl
Josefina Peña Mosca
Alina Peteranderl
Jingjing Wu
Sawako Tabuchi
Jan Hoffmann
Ann-Kathrin Karl
Axel Pagenstecher
Jörg Vogel
Andreas Beilhack
James B. Koprich
Jonathan M. Brotchie
Antoine-Emmanuel Saliba
Jens Volkmann
Chi Wang Ip
机构：
[1] University Hospital of Würzburg,Department of Neurology
[2] Technical University Munich,Institute of Neuronal Cell Biology
[3] Philipps University of Marburg,Department of Neuropathology
[4] Helmholtz-Center for Infection Research (HZI),Helmholtz Institute for RNA
[5] Würzburg University Hospital,based Infection Research (HIRI)
[6] Atuka Inc.,Department of Internal Medicine II, Center for Experimental Molecular Medicine (ZEMM)
[7] University Health Network,Krembil Research Institute, Toronto Western Hospital
[8] University of Würzburg,Faculty of Medicine, Institute of Molecular Infection Biology (IMIB)
来源：
Nature Communications | / 14卷
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摘要：
Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson’s disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn aggregations are contained within CD11c+ cells. Using single-cell RNA sequencing, we demonstrate that ileal CD11c+ cells are microglia-like and the same subtype of cells is activated in the brain and ileum of PD mice. Moreover, by utilizing mice expressing the photo-convertible protein, Dendra2, we show that CD11c+ cells traffic from the brain to the ileum. Together these data provide a mechanism of αSyn trafficking between the brain and gut.
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