{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:37:59Z","timestamp":1774312679437,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"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":[[2000,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The concerted action of several cytokines is necessary for resolution of both primary and secondary infection with Histoplasma capsulatum. Among the soluble factors that contribute to tissue sterilization, TNF-\u03b1 stands as a central mediator of protective immunity to this fungus. In this study, we explored the regulation of protective immunity by TNFR1 and -2. In primary pulmonary infection, both TNFR1\u2212\/\u2212 and -2\u2212\/\u2212 mice manifested a high mortality after infection with H. capsulatum, although TNFR1\u2212\/\u2212 mice were more susceptible than TNFR2 \u2212\/\u2212 mice. Overwhelming infection in the former was associated with a pronounced decrement in the number of inflammatory cells in the lungs and elevated IFN-\u03b3 and TNF-\u03b1 levels in the lungs. In contrast, IFN-\u03b3 levels were markedly decreased in TNFR2\u2212\/\u2212 mice, and treatment with this cytokine restored protective immunity. Lung macrophages from both groups of knockout mice released substantial amounts of NO. Upon secondary infection, TNFR2\u2212\/\u2212 mice survived rechallenge and cleared infection as efficiently as C57BL\/6 animals. In contrast, mice given mAb to TNFR1 succumbed to reexposure, and the high mortality was accompanied by a significant increase in fungal burden in the lungs. Both IL-4 and IL-10 were elevated in the lungs of these mice. The results demonstrate the pivotal influence of TNFR1 and -2 in controlling primary infection and highlight the differences between these receptors for regulation reexposure histoplasmosis.<\/jats:p>","DOI":"10.4049\/jimmunol.165.5.2657","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T17:58:09Z","timestamp":1398189489000},"page":"2657-2664","source":"Crossref","is-referenced-by-count":45,"title":["Regulation of Infection with\n                    <i>Histoplasma capsulatum<\/i>\n                    by TNFR1 and -2"],"prefix":"10.1093","volume":"165","author":[{"given":"Ruth","family":"Allendoerfer","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, University of Cincinnati College of Medicine , Cincinnati, OH 45267"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"George S","family":"Deepe","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Cincinnati College of Medicine , Cincinnati, OH 45267"},{"name":"Veterans Affairs Hospital , Cincinnati, OH 45219"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,9,1]]},"reference":[{"key":"2026020213072341300_R1","first-page":"254","volume-title":"Principles and Practices of Infectious Diseases","year":"2000"},{"key":"2026020213072341300_R2","first-page":"1349","volume-title":"J. 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