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

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

Nature communications (2020-05-13)
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 Jacobsen, Olaf Kniemeyer, Berit Jungnickel, Peter F Zipfel, Christine Skerka
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-TGFBR2 antibody produced in rabbit, IgG fraction of antiserum
Sigma-Aldrich
Anti-Complement C3b/iC3b Antibody, clone 6C9, clone 6C9, from mouse
Sigma-Aldrich
Duolink® In Situ Red Starter Kit Mouse/Rabbit