%0 Journal Article %T Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties %+ Institut Armand Frappier (INRS-IAF) %+ Centre for Host-Parasite Interaction [Montreal] (CHPI) %+ Institute of Parasitology [Sainte-Anne-de-Bellevue] %+ McGill University = Université McGill [Montréal, Canada] %+ The McDonnell Genome Institute (MGI) %+ USDA Agricultural Research Service [Maricopa, AZ] (USDA) %+ Tufts Medical Center [Boston] %+ Washington University in Saint Louis (WUSTL) %A Leroux, Louis-Philippe %A Nasr, Mohamad %A Valanparambil, Rajesh %A Tam, Mifong %A Rosa, Bruce, A. %A Siciliani, Elizabeth %A Hill, Dolores, E. %A Zarlenga, Dante %A Jaramillo, Maritza %A Weinstock, Joel %A Geary, Timothy, G. %A Stevenson, Mary, M. %A Urban, Joseph, F. %A Mitreva, Makedonka %A Jardim, Armando %Z Research was supported in part from a grant from Natural Sciences and Engineering Research Council of Canada Discovery Grant #238249, (A.J.) and Canadian Institutes of Health Research grants to (A.J., M.M.S.). The work at Washington University was supported by NIH grants AI081803 and GM097435 to M.M. The work at the USDA was supported by ARS Research Project 1265-32000-094-00D. %< avec comité de lecture %@ 2045-2322 %J Scientific Reports %I Nature Publishing Group %V 8 %N 1 %P 15921 %8 2018-10 %D 2018 %R 10.1038/s41598-018-34174-4 %M 30374177 %Z Life Sciences [q-bio]/ImmunologyJournal articles %X Parasitic worms have a remarkable ability to modulate host immune responses through several mechanisms including excreted/secreted proteins (ESP), yet the exact nature of these proteins and their targets often remains elusive. Here, we performed mass spectrometry analyses of ESP (TsESP) from larval and adult stages of the pig whipworm Trichuris suis (Ts) and identified ~350 proteins. Transcriptomic analyses revealed large subsets of differentially expressed genes in the various life cycle stages of the parasite. Exposure of bone marrow-derived macrophages and dendritic cells to TsESP markedly diminished secretion of the pro-inflammatory cytokines TNFα and IL-12p70. Conversely, TsESP exposure strongly induced release of the anti-inflammatory cytokine IL-10, and also induced high levels of nitric oxide (NO) and upregulated arginase activity in macrophages. Interestingly, TsESP failed to directly induce CD4+ CD25+ FoxP3+ regulatory T cells (Treg cells), while OVA-pulsed TsESP-treated dendritic cells suppressed antigen-specific OT-II CD4+ T cell proliferation. Fractionation of TsESP identified a subset of proteins that promoted anti-inflammatory functions, an activity that was recapitulated using recombinant T. suis triosephosphate isomerase (TPI) and nucleoside diphosphate kinase (NDK). Our study helps illuminate the intricate balance that is characteristic of parasite-host interactions at the immunological interface, and further establishes the principle that specific parasite-derived proteins can modulate immune cell functions. %G English %Z We wish to acknowledge Daniel Defoy at the Proteomics Platform of the Quebec Genomics Center part of the Centre de Recherche du Centre Hospitalier de l’Université Laval (CRCHUL) (Quebec City, QC, Canada) for performing the LC-MS/MS analyses. %2 https://riip.hal.science/pasteur-02136071/document %2 https://riip.hal.science/pasteur-02136071/file/Analysis_of_the_Trichuris_suis_excretory.pdf %L pasteur-02136071 %U https://riip.hal.science/pasteur-02136071 %~ RIIP %~ INRS-IAF