Immune modulation by complement receptor 3-dependent human monocyte TGF-ß1-transporting vesicles.

Halder LD, Jo EAH, Hasan MZ, Ferreira-Gomes M, Krüger T, Westermann M, Palme DI, Rambach G, Beyersdorf N, Speth C, Jacobsen ID, Kniemeyer O, Jungnickel B, Zipfel PF, Skerka C (2020) Immune modulation by complement receptor 3-dependent human monocyte TGF-ß1-transporting vesicles. Nat Commun 11(1), 2331.

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.

Leibniz-HKI-Authors

Luke Donald Halder
Md Zahidul Hasan
Ilse Denise Jacobsen
Emeraldo Jo
Olaf Kniemeyer
Thomas Krüger
Diana Palme
Christine Skerka
Peter F. Zipfel

Identifier

doi: 10.1038/s41467-020-16241-5

PMID: 32393780