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Thus, comparing the immune response in hosts that develop different degrees of disease severity represents a promising approach to discover processes contributing to trypanosomiasis control. It is known that limitation of pathogenicity requires a transition in the course of infection, from an IFN-\u03b3-dependent response resulting in the development of classically activated myeloid cells (M1), to a counterbalancing IL-10-dependent response associated with alternatively activated myeloid cells (M2). Herein, mechanisms and downstream effectors by which M2 contribute to lower the pathogenicity and the associated susceptibility to African trypanosomiasis have been explored. Gene expression analysis in IL-10 knockout and wild-type mice, that are susceptible and relatively resistant to Trypanosoma congolense infection, respectively, revealed a number of IL-10-inducible genes expressed by M2, including Sepp1 coding for selenoprotein P. Functional analyses confirm that selenoprotein P contributes to limit disease severity through anti-oxidant activity. Indeed, Sepp1 knockout mice, but not Sepp1\u0394240-361 mice retaining the anti-oxidant motif but lacking the selenium transporter domain of selenoprotein P, exhibited increased tissue injury that associated with increased production of reactive oxygen species and increased apoptosis in the liver immune cells, reduced parasite clearance capacity of myeloid cells, and decreased survival. These data validate M2-associated molecules as functioning in reducing the impact of parasite infection on the host.<\/jats:p>","DOI":"10.4049\/jimmunol.180.9.6168","type":"journal-article","created":{"date-parts":[[2014,4,23]],"date-time":"2014-04-23T19:58:20Z","timestamp":1398283100000},"page":"6168-6175","source":"Crossref","is-referenced-by-count":85,"title":["Alternatively Activated Myeloid Cells Limit Pathogenicity Associated with African Trypanosomiasis through the IL-10 Inducible Gene Selenoprotein P"],"prefix":"10.1093","volume":"180","author":[{"given":"Tom","family":"Bosschaerts","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]},{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Guilliams","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]},{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Noel","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]},{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"He\u0301rin","sequence":"additional","affiliation":[{"name":"Cell and Tissue Laboratory, Unite\u0301 de Recherche en Physiologie Mole\u0301culaire, Faculte\u0301s Universitaires Notre-Dame de la Paix , Namur ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F","family":"Burk","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina E","family":"Hill","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Brys","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]},{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Raes","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]},{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholamreza Hassanzadeh","family":"Ghassabeh","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]},{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"De Baetselier","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]},{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Beschin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]},{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,5,1]]},"reference":[{"key":"2026012809195679700_R1","first-page":"14","volume-title":"Eur. 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