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We herein start to elucidate the molecular basis of C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mouse resistance to <jats:italic>S<\/jats:italic>.\u00a0<jats:italic>mansoni<\/jats:italic> following treatment with the cysteine peptidase, papain. We evaluated the early cytokine signals delivered by epidermal, dermal, and draining lymph node cells of na\u00efve, and <jats:italic>S<\/jats:italic>.\u00a0<jats:italic>mansoni<\/jats:italic> \u2010infected mice treated 1\u00a0day earlier with 0 or 50\u00a0<jats:italic>\u03bc<\/jats:italic>g papain, or immunized twice with papain only (10\u00a0<jats:italic>\u03bc<\/jats:italic>g\/mouse), papain\u2010free recombinant <jats:italic>S<\/jats:italic>.\u00a0<jats:italic>mansoni<\/jats:italic> glyceraldehyde 3\u2010phosphate dehydrogenase and 2\u2010Cys peroxiredoxin peptide (10 and 15\u00a0<jats:italic>\u03bc<\/jats:italic>g\/mouse, respectively\u00a0=\u00a0antigen Mix), or papain\u2010adjuvanted antigen Mix. <jats:italic>Schistosoma mansoni<\/jats:italic> infection induced epidermal and lymph node cells to release type 1, type 2 and type 17 cytokines, known to counteract each other. Expectedly, humoral immune responses were negligible until patency. Papain pretreatment or papain\u2010based vaccination diminished or shut off <jats:italic>S<\/jats:italic>.\u00a0<jats:italic>mansoni<\/jats:italic> infection early induction of type 1, type 17 and type 2 cytokines except for thymic stromal lymphopoietin and programmed the immune system towards a polarized type 2 immune milieu, associated with highly significant (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.005 \u2013 &lt;0.0001) resistance to <jats:italic>S<\/jats:italic>.\u00a0<jats:italic>mansoni<\/jats:italic> infection.<\/jats:p>","DOI":"10.1111\/sji.12399","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T12:30:53Z","timestamp":1448454653000},"page":"128-138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Papain\u2010Based Vaccination Modulates <i>Schistosoma mansoni<\/i> Infection\u2010Induced Cytokine Signals"],"prefix":"10.1111","volume":"83","author":[{"given":"N.","family":"Abdel Aziz","sequence":"first","affiliation":[{"name":"Chemistry Department Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Tallima","sequence":"additional","affiliation":[{"name":"Zoology Department Faculty of Science Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. 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