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

• Published in: PLoS neglected tropical diseases Vol. 17; no. 6; p. e0011344
• Main Authors: Chayé, Mathilde A. M., Gasan, Thomas A., Ozir-Fazalalikhan, Arifa, Scheenstra, Maaike R., Zawistowska-Deniziak, Anna, van Hengel, Oscar R. J., Gentenaar, Max, Manurung, Mikhael D., Harvey, Michael R., Codée, Jeroen D. C., Chiodo, Fabrizio, Heijke, Anouk M., Kalinowska, Alicja, van Diepen, Angela, Hensbergen, Paul J., Yazdanbakhsh, Maria, Guigas, Bruno, Hokke, Cornelis H., Smits, Hermelijn H.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2023
• Subjects: Affinity chromatography; Analysis; Animals; Antibodies; Antigens; Arthritis; Autoimmune diseases; Biology and Life Sciences; Cancer; Cells; Chromatography; Chronic illnesses; Cytokines; Eggs; Experiments; Fatty acid-binding protein; Fatty acids; Flow cytometry; Glycan; Glycoproteins; Immune response; Immune system; Immunity; Immunological diseases; Immunomodulation; Infections; Inflammatory bowel disease; Interleukin 10; Interleukins; Low molecular weights; Lymphocytes B; Medical innovations; Medicine and Health Sciences; Molecular weight; Molecules; Nanoparticles; Penicillin; Polysaccharides; Prevention; Proteins; Proteomics; Recombinants; Research and Analysis Methods; Risk factors; Schistosoma mansoni; Schistosomiasis; Size exclusion chromatography; Software; Thioredoxin; Tropical diseases; Netherlands
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0011344

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 fractions able to induce IL-10 production by B cells (out of 18) in the high, medium and low molecular weight (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 and hock immunizations with recombinant SmTrx1 and Sm14 showed their ability to dose-dependently induce IL-10 production by B cells both in vitro and in vivo . Identification of unique Breg cells-inducing molecules may pave the way to innovative therapeutic strategies for inflammatory and auto-immune diseases.