{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:02:13Z","timestamp":1790413333762,"version":"4.1.0"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"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":[[2016,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypoxia-inducible factor (HIF)-1\u03b1 is a transcription factor that regulates metabolic and immune response genes in the setting of low oxygen tension and inflammation. We investigated the function of HIF-1\u03b1 in the host response to Histoplasma capsulatum because granulomas induced by this pathogenic fungus develop hypoxic microenvironments during the early adaptive immune response. In this study, we demonstrated that myeloid HIF-1\u03b1\u2013deficient mice exhibited elevated fungal burden during the innate immune response (prior to 7 d postinfection) as well as decreased survival in response to a sublethal inoculum of H. capsulatum. The absence of myeloid HIF-1\u03b1 did not alter immune cell recruitment to the lungs of infected animals but was associated with an elevation of the anti-inflammatory cytokine IL-10. Treatment with mAb to IL-10 restored protective immunity to the mutant mice. Macrophages (M\u03d5s) constituted most IL-10\u2013producing cells. Deletion of HIF-1\u03b1 in neutrophils or dendritic cells did not alter fungal burden, thus implicating M\u03d5s as the pivotal cell in host resistance. HIF-1\u03b1 was stabilized in M\u03d5s following infection. Increased activity of the transcription factor CREB in HIF-1\u03b1\u2013deficient M\u03d5s drove IL-10 production in response to H. capsulatum. IL-10 inhibited M\u03d5 control of fungal growth in response to the activating cytokine IFN-\u03b3. Thus, we identified a critical function for M\u03d5 HIF-1\u03b1 in tempering IL-10 production following infection. We established that transcriptional regulation of IL-10 by HIF-1\u03b1 and CREB is critical for activation of M\u03d5s by IFN-\u03b3 and effective handling of H. capsulatum.<\/jats:p>","DOI":"10.4049\/jimmunol.1600342","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T03:23:46Z","timestamp":1465269826000},"page":"565-579","source":"Crossref","is-referenced-by-count":37,"title":["Inverse Correlation between IL-10 and HIF-1\u03b1 in Macrophages Infected with <i>Histoplasma capsulatum<\/i>"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7565-7216","authenticated-orcid":false,"given":"Roger A","family":"Fecher","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, University of Cincinnati College of Medicine , Cincinnati, OH 45267"},{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati , Cincinnati, OH 45220"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C","family":"Horwath","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Cincinnati College of Medicine , Cincinnati, OH 45267"},{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati , Cincinnati, OH 45220"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8812-489X","authenticated-orcid":false,"given":"Dirk","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rupp","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6158-6461","authenticated-orcid":false,"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":"Medical Service, Veterans Affairs Hospital , Cincinnati, OH 45220"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,7,15]]},"reference":[{"key":"2025030617464287800_r1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1086\/500405","article-title":"Hospitalizations for endemic mycoses: a population-based national study","volume":"42","author":"Chu","year":"2006","journal-title":"Clin. 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