Immune Modulation by Complement Receptor 3-dependent Human Monocyte TGF-β1-transporting Vesicles

Overview

Journal Nat Commun

Specialty Biology

Date 2020 May 13

PMID 32393780

Citations 30

Authors

Luke D Halder

Emeraldo A H Jo

Mohammad Z Hasan

Marta Ferreira-Gomes

Thomas Kruger

Martin Westermann

Diana I Palme

Gunter Rambach

Niklas Beyersdorf

Cornelia Speth

Ilse D Jacobsen

Olaf Kniemeyer

Berit Jungnickel

Peter F Zipfel

Christine Skerka

Affiliations

Soon will be listed here.

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.

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