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Immune modulation by complement receptor 3-dependent human monocyte TGF-β1-transporting vesicles

Author

Listed:
  • Luke D. Halder

    (Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology)

  • Emeraldo A. H. Jo

    (Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology)

  • Mohammad Z. Hasan

    (Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology)

  • Marta Ferreira-Gomes

    (Department of Cell Biology, Institute of Biochemistry and Biophysics, Friedrich Schiller University)

  • Thomas Krüger

    (Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology)

  • Martin Westermann

    (Electron Microscopy Center, University Hospital Jena)

  • Diana I. Palme

    (Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology)

  • Günter Rambach

    (Division of Hygiene and Medical Microbiology, Medical University of Innsbruck)

  • Niklas Beyersdorf

    (Institute for Virology and Immunobiology, University of Würzburg)

  • Cornelia Speth

    (Division of Hygiene and Medical Microbiology, Medical University of Innsbruck)

  • Ilse D. Jacobsen

    (Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology
    Friedrich Schiller University)

  • Olaf Kniemeyer

    (Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology)

  • Berit Jungnickel

    (Department of Cell Biology, Institute of Biochemistry and Biophysics, Friedrich Schiller University)

  • Peter F. Zipfel

    (Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology
    Friedrich Schiller University)

  • Christine Skerka

    (Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology)

Abstract

Extracellular vesicles have an important function in cellular communication. Here, we show that human and mouse monocytes release TGF-β1-transporting vesicles in response to the pathogenic fungus Candida albicans. Soluble β-glucan from C. albicans binds to complement receptor 3 (CR3, also known as CD11b/CD18) on monocytes and induces the release of TGF-β1-transporting vesicles. CR3-dependence is demonstrated using CR3-deficient (CD11b knockout) monocytes generated by CRISPR-CAS9 genome editing and isolated from CR3-deficient (CD11b knockout) mice. These vesicles reduce the pro-inflammatory response in human M1-macrophages as well as in whole blood. Binding of the vesicle-transported TGF-β1 to the TGF-β receptor inhibits IL1B transcription via the SMAD7 pathway in whole blood and induces TGFB1 transcription in endothelial cells, which is resolved upon TGF-β1 inhibition. Notably, human complement-opsonized apoptotic bodies induce production of similar TGF-β1-transporting vesicles in monocytes, suggesting that the early immune response might be suppressed through this CR3-dependent anti-inflammatory vesicle pathway.

Suggested Citation

  • Luke D. Halder & Emeraldo A. H. Jo & Mohammad Z. Hasan & Marta Ferreira-Gomes & Thomas Krüger & Martin Westermann & Diana I. Palme & Günter Rambach & Niklas Beyersdorf & Cornelia Speth & Ilse D. Jacob, 2020. "Immune modulation by complement receptor 3-dependent human monocyte TGF-β1-transporting vesicles," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16241-5
    DOI: 10.1038/s41467-020-16241-5
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