Dataset Information

Immune modulation by complement receptor 3 (CD18/CD11b) dependent human monocyte TGF-β1-transporting vesicles

ABSTRACT: Extracellular vesicles play an important role in human cellular communication. Here, we show that human and mouse monocytes release TGF-β1-transporting vesicles in response to the pathogenic fungus Candida albicans. Soluble beta-glucan from Candida albicans binds to complement receptor 3 (CR3, 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. Isolated vesicles dampen 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 IL-1β gene transcription via the SMAD7 pathway in whole blood and induces TGF-β1 transcription in endothelial cells. Inhibition of TGF-β1 relieved the suppression of such proinflammatory effect. Notably, human opsonized apoptotic bodies induce similar TGF-β1-transporting vesicles in monocytes, suggesting that the early immune response is suppressed through this newly identified CR3-dependent anti-inflammatory vesicle pathway.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Blood

SUBMITTER: Thomas Krüger

LAB HEAD: Olaf Kniemeyer

PROVIDER: PXD015780 | Pride | 2020-04-22

REPOSITORIES: Pride

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Publications

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

Halder Luke D LD Jo Emeraldo A H EAH Hasan Mohammad Z MZ Ferreira-Gomes Marta M Krüger Thomas T Westermann Martin M Palme Diana I DI Rambach Günter G Beyersdorf Niklas N Speth Cornelia C Jacobsen Ilse D ID Kniemeyer Olaf O Jungnickel Berit B Zipfel Peter F PF Skerka Christine C

Nature communications 20200511 1

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 a ...[more]

PMID: 32393780

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Dataset Information

Immune modulation by complement receptor 3 (CD18/CD11b) dependent human monocyte TGF-β1-transporting vesicles

Publications

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

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