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

Author

Listed:
  • Rhonda L. McFleder

    (University Hospital of Würzburg)

  • Anastasiia Makhotkina

    (University Hospital of Würzburg)

  • Janos Groh

    (Technical University Munich)

  • Ursula Keber

    (Philipps University of Marburg)

  • Fabian Imdahl

    (Helmholtz-Center for Infection Research (HZI))

  • Josefina Peña Mosca

    (Würzburg University Hospital)

  • Alina Peteranderl

    (University Hospital of Würzburg)

  • Jingjing Wu

    (University Hospital of Würzburg)

  • Sawako Tabuchi

    (University Hospital of Würzburg)

  • Jan Hoffmann

    (University Hospital of Würzburg)

  • Ann-Kathrin Karl

    (University Hospital of Würzburg)

  • Axel Pagenstecher

    (Philipps University of Marburg)

  • Jörg Vogel

    (Helmholtz-Center for Infection Research (HZI))

  • Andreas Beilhack

    (Würzburg University Hospital)

  • James B. Koprich

    (Atuka Inc.
    University Health Network)

  • Jonathan M. Brotchie

    (Atuka Inc.
    University Health Network)

  • Antoine-Emmanuel Saliba

    (Helmholtz-Center for Infection Research (HZI)
    University of Würzburg)

  • Jens Volkmann

    (University Hospital of Würzburg)

  • Chi Wang Ip

    (University Hospital of Würzburg)

Abstract

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.

Suggested Citation

  • 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, 2023. "Brain-to-gut trafficking of alpha-synuclein by CD11c+ cells in a mouse model of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43224-z
    DOI: 10.1038/s41467-023-43224-z
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    References listed on IDEAS

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    1. Changyoun Kim & Dong-Hwan Ho & Ji-Eun Suk & Sungyong You & Sarah Michael & Junghee Kang & Sung Joong Lee & Eliezer Masliah & Daehee Hwang & He-Jin Lee & Seung-Jae Lee, 2013. "Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    2. Minako Ito & Kyoko Komai & Setsuko Mise-Omata & Mana Iizuka-Koga & Yoshiko Noguchi & Taisuke Kondo & Ryota Sakai & Kazuhiko Matsuo & Takashi Nakayama & Osamu Yoshie & Hiroko Nakatsukasa & Shunsuke Chi, 2019. "Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery," Nature, Nature, vol. 565(7738), pages 246-250, January.
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