Schistosoma mansoni egg-derived thioredoxin and Sm14 drive the development of IL-10 producing regulatory B cells

ABSTRACT: During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing regulatory B (Breg) cells play a significant role. Schistosoma mansoni soluble egg antigens (SEA) are bound and internalized by B cells and induce both human and mouse IL-10 producing Breg cells. To identify Breg-inducing proteins in SEA, we fractionated SEA by size exclusion chromatography and found 6 active fractions (out of 18) in the high, medium and low MW range. The high MW fractions were rich in heavily glycosylated molecules, including multi-fucosylated proteins. Using SEA glycoproteins purified by affinity chromatography and synthetic glycans coupled to gold nanoparticles, we investigated the role of these glycan structures in inducing IL-10 production by B cells. Then, we performed proteomics analysis on active low MW fractions and identified a number of proteins with putative immunomodulatory properties, notably thioredoxin (SmTrx1) and the fatty acid binding protein Sm14. Subsequent splenic murine B cell stimulations with recombinant SmTrx1 and Sm14 showed their ability to dose-dependently induce IL-10 production and FoxP3 Treg cell priming by B cells. Identification of unique Breg cells-inducing molecules may pave the way to innovative therapeutic strategies for inflammatory and auto-immune diseases.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Schistosoma Mansoni (blood Fluke)

TISSUE(S): Egg

SUBMITTER: Paul Hensbergen  

LAB HEAD: Paul Hensbergen

PROVIDER: PXD031333 | Pride | 2023-10-24

REPOSITORIES: Pride