Immune modulation by complement receptor 3-dependent human monocyte TGF-β1-transporting vesicles
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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Enthalten in: |
Nature communications - 11(2020), 1 vom: 11. Mai, Seite 2331 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Halder, Luke D [VerfasserIn] |
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Links: |
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Themen: |
Beta-Glucans |
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Anmerkungen: |
Date Completed 05.08.2020 Date Revised 11.05.2021 published: Electronic Citation Status MEDLINE |
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doi: |
10.1038/s41467-020-16241-5 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM309769248 |
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520 | |a 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 | ||
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700 | 1 | |a Krüger, Thomas |e verfasserin |4 aut | |
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700 | 1 | |a Kniemeyer, Olaf |e verfasserin |4 aut | |
700 | 1 | |a Jungnickel, Berit |e verfasserin |4 aut | |
700 | 1 | |a Zipfel, Peter F |e verfasserin |4 aut | |
700 | 1 | |a Skerka, Christine |e verfasserin |4 aut | |
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