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

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

Nature communications - 11(2020), 1 vom: 11. Mai, Seite 2331

Sprache:

Englisch

Beteiligte Personen:

Halder, Luke D [VerfasserIn]
Jo, Emeraldo A H [VerfasserIn]
Hasan, Mohammad Z [VerfasserIn]
Ferreira-Gomes, Marta [VerfasserIn]
Krüger, Thomas [VerfasserIn]
Westermann, Martin [VerfasserIn]
Palme, Diana I [VerfasserIn]
Rambach, Günter [VerfasserIn]
Beyersdorf, Niklas [VerfasserIn]
Speth, Cornelia [VerfasserIn]
Jacobsen, Ilse D [VerfasserIn]
Kniemeyer, Olaf [VerfasserIn]
Jungnickel, Berit [VerfasserIn]
Zipfel, Peter F [VerfasserIn]
Skerka, Christine [VerfasserIn]

Links:

Volltext

Themen:

Beta-Glucans
Interleukin-6
Journal Article
Macrophage-1 Antigen
Research Support, Non-U.S. Gov't
TGFB1 protein, human
Transforming Growth Factor beta1

Anmerkungen:

Date Completed 05.08.2020

Date Revised 11.05.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-020-16241-5

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM309769248