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Serine protease inhibitors (serpins) play an important role in ES product-mediated immunoregulatory effects during T. spiralis infection. In this study, the immunoregulatory properties of a serpin derived from T. spiralis (Ts-serpin) were explored in BALB\/c mice. The results showed that naturally occurring Ts-serpin was detected in the stichosomes of muscle larvae and adult worms. Moreover, enhancing (by injection of a soluble-expressed recombinant Ts-serpin [rTs-serpin]) or blocking (by passive immunization with anti\u2013rTs-serpin serum) the effects of Ts-serpin changed the levels of cytokines related to inflammation induced by T. spiralis infection in the serum, mesenteric lymph nodes, and peritoneal cavity, which then led to a change in the adult worm burden in early T. spiralis infection. Moreover, the phenotypic changes in peritoneal macrophages were found to be related to Ts-serpin\u2013mediated immunoregulation. Furthermore, a STAT6 activation mechanism independent of IL-4R\u03b1 has been found to regulate protein-mediated alternative activation of bone marrow\u2013derived macrophages and mimic the immunoregulatory role of Ts-serpin in T. spiralis infection. Finally, the anti-inflammatory properties of rTs-serpin and bone marrow\u2013derived macrophage alternative activation by rTs-serpin were demonstrated using a trinitrobenzene sulfonic acid\u2013induced inflammatory bowel disease model. In summary, a protein-triggered anti-inflammatory mechanism was found to favor the survival of T. spiralis in the early stage of infection and help to elucidate the immunoregulatory effects of T. spiralis on the host immune response.<\/jats:p>","DOI":"10.4049\/jimmunol.2000290","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T22:30:17Z","timestamp":1613514617000},"page":"963-977","source":"Crossref","is-referenced-by-count":33,"title":["The Anti-Inflammatory Immune Response in Early <i>Trichinella spiralis<\/i> Intestinal Infection Depends on Serine Protease Inhibitor\u2013Mediated Alternative Activation of Macrophages"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5286-747X","authenticated-orcid":false,"given":"Ning","family":"Xu","sequence":"first","affiliation":[{"name":"Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University , Changchun 130062 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University , Changchun 130062 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University , Changchun 130062 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaming","family":"Yang","sequence":"additional","affiliation":[{"name":"Yunnan Institute of Parasitic Diseases , Pu\u2019er City, Yunnan 665000 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V\u00e9t\u00e9rinaire d\u2019Alfort, Institut National de Recherche pour l\u2019Agriculture, l\u2019Alimentation et l\u2019Environnement, Universit\u00e9 Paris-Est, Laboratoire de Sant\u00e9 Animale , 94706 Maisons-Alfort ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3998-7792","authenticated-orcid":false,"given":"Pascal","family":"Boireau","sequence":"additional","affiliation":[{"name":"UMR de Biologie Mol\u00e9culaire et d\u2019Immunologie Parasitaires, Agence Nationale de S\u00e9curit\u00e9 Sanitaire de l\u2019Alimentation, de l\u2019Environnement et du Travail, \u00c9cole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Institut National de Recherche pour l\u2019Agriculture, l\u2019Alimentation et l\u2019Environnement, Universit\u00e9 Paris-Est, Laboratoire de Sant\u00e9 Animale , 94706 Maisons-Alfort 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