Extracellular vesicles have an important function in cellular communication. Here, we show that human and mouse monocytes release TGF-beta1-transporting vesicles in response to the pathogenic fungus Candida albicans. Soluble beta-glucan from C. albicans binds to complement receptor 3 (CR3, also known as CD11b/CD18) on monocytes and induces the release of TGF-beta1-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-beta1 to the TGF-beta receptor inhibits IL1B transcription via the SMAD7 pathway in whole blood and induces TGFB1 transcription in endothelial cells, which is resolved upon TGF-beta1 inhibition. Notably, human complement-opsonized apoptotic bodies induce production of similar TGF-beta1-transporting vesicles in monocytes, suggesting that the early immune response might be suppressed through this CR3-dependent anti-inflammatory vesicle pathway.
PubMed ID: 32393780
Projects: C4 (E)
Journal: Nat Commun
Citation: Nat Commun. 2020 May 11;11(1):2331. doi: 10.1038/s41467-020-16241-5.
Date Published: 11th May 2020
Created: 18th Feb 2021 at 11:05