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While early effector T cell responses are required for limiting parasitemia, these responses need to be switched off by regulatory mechanisms in a timely manner to avoid immune-mediated tissue damage. Interleukin-10 receptor (IL-10R) signaling is considered to be a vital component of regulatory responses, although its role in host resistance to severe immune pathology during acute malaria infections is not fully understood. In this study, we have determined the contribution of IL-10R signaling to the regulation of immune responses during<jats:named-content content-type=\"genus-species\">Plasmodium berghei<\/jats:named-content>ANKA-induced experimental cerebral malaria (ECM). We show that antibody-mediated blockade of the IL-10R during<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>ANKA infection in ECM-resistant BALB\/c mice leads to amplified T cell activation, higher serum gamma interferon (IFN-\u03b3) concentrations, enhanced intravascular accumulation of both parasitized red blood cells and CD8<jats:sup>+<\/jats:sup>T cells to the brain, and an increased incidence of ECM. Importantly, the pathogenic effects of IL-10R blockade during<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>ANKA infection were reversible by depletion of T cells and neutralization of IFN-\u03b3. Our findings underscore the importance of IL-10R signaling in preventing T-cell- and cytokine-mediated pathology during potentially lethal malaria infections.<\/jats:p>","DOI":"10.1128\/iai.00941-16","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:30:30Z","timestamp":1491870630000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Host Resistance to Plasmodium-Induced Acute Immune Pathology Is Regulated by Interleukin-10 Receptor Signaling"],"prefix":"10.1128","volume":"85","author":[{"given":"Carla","family":"Claser","sequence":"first","affiliation":[{"name":"Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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