{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:22Z","timestamp":1787030842272,"version":"build-2736575974"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The potent immunoregulatory properties of IL-10 can counteract protective immune responses and, thereby, promote persistent infections, as evidenced by studies of cryptococcal lung infection in IL-10\u2013deficient mice. To further investigate how IL-10 impairs fungal clearance, the current study used an established murine model of C57BL\/6J mice infected with Cryptococcus neoformans strain 52D. Our results demonstrate that fungal persistence is associated with an early and sustained expression of IL-10 by lung leukocytes. To examine whether IL-10\u2013mediated immune modulation occurs during the early or late phase of infection, assessments of fungal burden and immunophenotyping were performed on mice treated with anti\u2013IL-10R\u2013blocking Ab at 3, 6, and 9 d postinfection (dpi) (early phase) or at 15, 18, and 21 dpi (late phase). We found that both early and late IL-10 blockade significantly improved fungal clearance within the lung compared with isotype control treatment when assessed 35 dpi. Immunophenotyping identified that IL-10 blockade enhanced several critical effector mechanisms, including increased accumulation of CD4+ T cells and B cells, but not CD8+ T cells; specific increases in the total numbers of Th1 and Th17 cells; and increased accumulation and activation of CD11b+ dendritic cells and exudate macrophages. Importantly, IL-10 blockade effectively abrogated dissemination of C. neoformans to the brain. Collectively, this study identifies early and late cellular and molecular mechanisms through which IL-10 impairs fungal clearance and highlights the therapeutic potential of IL-10 blockade in the treatment of fungal lung infections.<\/jats:p>","DOI":"10.4049\/jimmunol.1400650","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T03:38:37Z","timestamp":1410838717000},"page":"4107-4116","source":"Crossref","is-referenced-by-count":52,"title":["Early or Late IL-10 Blockade Enhances Th1 and Th17 Effector Responses and Promotes Fungal Clearance in Mice with Cryptococcal Lung Infection"],"prefix":"10.1093","volume":"193","author":[{"given":"Benjamin J","family":"Murdock","sequence":"first","affiliation":[{"name":"Research Service, Veterans Affairs Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI 48105"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seagal","family":"Teitz-Tennenbaum","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI 48105"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwo-Hsiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI 48105"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Dils","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI 48105"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni N","family":"Malachowski","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI 48105"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L","family":"Curtis","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"},{"name":"Pulmonary Section, Medical Service, Veterans Affairs Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI 48105"},{"name":"Graduate Program in Immunology, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal A","family":"Olszewski","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI 48105"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"},{"name":"Graduate Program in Immunology, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Osterholzer","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"},{"name":"Pulmonary Section, Medical Service, Veterans Affairs Ann Arbor Healthcare System, Department of Veterans Affairs Health System , Ann Arbor, MI 48105"},{"name":"Graduate Program in Immunology, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,10,15]]},"reference":[{"key":"2025030707405588600_r1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1513\/pats.200907-063AL","article-title":"Cryptococcus","volume":"7","author":"Li","year":"2010","journal-title":"Proc. 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