{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:57:09Z","timestamp":1787021829786,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013554","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI079293"],"award-info":[{"award-number":["R01 AI079293"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI079293"],"award-info":[{"award-number":["R01 AI079293"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI079293"],"award-info":[{"award-number":["R01 AI079293"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI164746"],"award-info":[{"award-number":["R01 AI164746"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI164746"],"award-info":[{"award-number":["R01 AI164746"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Subclinical parasitemia constitutes the predominant proportion of\n                    <jats:italic>\n                      <jats:italic>Plasmodium<\/jats:italic>\n                    <\/jats:italic>\n                    spp. infections in hyperendemic regions of the world. Elevated levels of serum interleukin-10 (IL-10) are observed in both acute symptomatic and chronic subclinical\n                    <jats:italic>\n                      <jats:italic>Plasmodium<\/jats:italic>\n                    <\/jats:italic>\n                    spp. infections. The role of IL-10 in acute infection has been extensively studied; however, the role of sustained elevated levels of IL-10 in chronic subclinical plasmodial infections remains to be determined. We investigated the role of IL-10 in a long-term subclinical and patent\n                    <jats:italic>\n                      <jats:italic>Plasmodium chabaudi chabaudi-<\/jats:italic>\n                    <\/jats:italic>\n                    AS (\n                    <jats:italic>\n                      <jats:italic>Pc<\/jats:italic>\n                    <\/jats:italic>\n                    ) infection using mice lacking humoral immunity (\u00b5MT\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice).\n                    <jats:italic>\n                      <jats:italic>Pc<\/jats:italic>\n                    <\/jats:italic>\n                    -infected \u00b5MT\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice exhibit a long-term (99 days) chronic infection, with microscopic levels of parasitemia and without any outward signs of disease. We found that chronically infected mice have slightly elevated levels of tumor necrosis factor \u03b1 (TNF\u03b1) and interferon-\u03b3 (IFN\u03b3), and high levels of IL-10 in the circulation. The source of IL-10 was CD4+\u2009T cells. We found that elevated IL-10 levels were mechanistically linked to subclinical\n                    <jats:italic>\n                      <jats:italic>Plasmodium<\/jats:italic>\n                    <\/jats:italic>\n                    infection by blocking IL-10 signaling. Anti-IL-10R resulted in a marked, albeit transient, reduction of the parasitemia that was accompanied by a robust pro-inflammatory response and death of chronically infected \u00b5MT\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice. A similar outcome was observed in infected \u00b5MT\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice after CD4+\u2009T cell depletion with anti-CD4 antibody. CD4-depleted infected \u00b5MT\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice exhibited reduced IL-10 and rapid weight loss, succumbing to infection by day 6 after CD4 neutralization. Our results showed that IL-10 from CD4+\u2009T cells limits immune-mediated pathology in chronic subclinical\n                    <jats:italic>\n                      <jats:italic>Pc<\/jats:italic>\n                    <\/jats:italic>\n                    infection in \u00b5MT\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice by protecting against excessive inflammatory responses to blood-stage parasites.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0013554","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T21:52:30Z","timestamp":1758318750000},"page":"e0013554","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Interleukin-10 limits immune-mediated pathology in chronic subclinical plasmodial infection"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8720-0088","authenticated-orcid":true,"given":"Leandro","family":"de Souza Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G.","family":"Monks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine S.","family":"Forconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet N.","family":"Crabtree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelsy","family":"De Paula Tamburro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn A.","family":"Kurt-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo 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