| First Author | Halder LD | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 2331 |
| PubMed ID | 32393780 | Mgi Jnum | J:292230 |
| Mgi Id | MGI:6447170 | Doi | 10.1038/s41467-020-16241-5 |
| Citation | Halder LD, et al. (2020) Immune modulation by complement receptor 3-dependent human monocyte TGF-beta1-transporting vesicles. Nat Commun 11(1):2331 |
| abstractText | 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. |
