In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 17, No. 6 ( 2023-6-26), p. e0011344-
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 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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0011344
DOI:
10.1371/journal.pntd.0011344.g001
DOI:
10.1371/journal.pntd.0011344.g002
DOI:
10.1371/journal.pntd.0011344.g003
DOI:
10.1371/journal.pntd.0011344.g004
DOI:
10.1371/journal.pntd.0011344.g005
DOI:
10.1371/journal.pntd.0011344.t001
DOI:
10.1371/journal.pntd.0011344.s001
DOI:
10.1371/journal.pntd.0011344.s002
DOI:
10.1371/journal.pntd.0011344.s003
DOI:
10.1371/journal.pntd.0011344.s004
DOI:
10.1371/journal.pntd.0011344.s005
DOI:
10.1371/journal.pntd.0011344.s006
DOI:
10.1371/journal.pntd.0011344.s007
DOI:
10.1371/journal.pntd.0011344.s008
DOI:
10.1371/journal.pntd.0011344.s009
DOI:
10.1371/journal.pntd.0011344.s010
DOI:
10.1371/journal.pntd.0011344.s011
DOI:
10.1371/journal.pntd.0011344.s012
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2429704-5
Permalink