{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:53:29Z","timestamp":1787504009034,"version":"build-2736575974"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2013,3,26]],"date-time":"2013-03-26T00:00:00Z","timestamp":1364256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In the murine model of pulmonary infection with Cryptococcus neoformans, IL-4 receptor \u03b1 (IL-4R\u03b1)-dependent polyfunctional Th2 cells induce disease progression associated with alternative activation of lung macrophages. To characterize the effector role of IL-4R\u03b1-dependent alternatively activated macrophages (aaMph), we intra-nasally infected mice with genetically ablated IL-4R\u03b1 expression on macrophages (LysMCreIL-4R\u03b1\u2013\/lox mice) and IL-4R\u03b1\u2013\/lox littermates. LysMCreIL-4R\u03b1\u2013\/lox mice were significantly more resistant to pulmonary cryptococcosis with higher survival rates and lower lung burden than non-deficient heterozygous littermates. Infected LysMCreIL-4R\u03b1\u2013\/lox mice had reduced but detectable numbers of aaMph expressing arginase-1, chitinase-like enzyme (YM1) and CD206. Similar pulmonary expression of inducible nitric oxide synthase was found in LysMCreIL-4R\u03b1\u2013\/lox and IL-4R\u03b1\u2013\/lox control mice, but macrophages from LysMCreIL-4R\u03b1\u2013\/lox mice showed a higher potential to produce nitric oxide. In contrast to the differences in the macrophage phenotype, pulmonary Th2 responses were similar in infected LysMCreIL-4R\u03b1\u2013\/lox and IL-4R\u03b1\u2013\/lox mice with each mouse strain harboring polyfunctional Th2 cells. Consistently, type 2 pulmonary allergic inflammation associated with eosinophil recruitment and epithelial mucus production was present in lungs of both LysMCreIL-4R\u03b1\u2013\/lox and IL-4R\u03b1\u2013\/lox mice. Our results demonstrate that, despite residual IL-4R\u03b1-independent alternative macrophage activation and ongoing Th2-dependent allergic inflammation, abrogation of IL-4R\u03b1-dependent aaMph is sufficient to confer resistance in pulmonary cryptococcosis. This is even evident on a relatively resistant heterozygous IL-4R\u03b1+\/\u2013 background indicating a key contribution of macrophage IL-4R\u03b1 expression to susceptibility in allergic bronchopulmonary mycosis.<\/jats:p>","DOI":"10.1093\/intimm\/dxt003","type":"journal-article","created":{"date-parts":[[2013,3,26]],"date-time":"2013-03-26T22:13:13Z","timestamp":1364335993000},"page":"459-470","source":"Crossref","is-referenced-by-count":35,"title":["Abrogation of IL-4 receptor-\u03b1-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing Th2 response"],"prefix":"10.1093","volume":"25","author":[{"given":"Uwe","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Institute of Immunology\/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig 1 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Stenzel","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin 2 , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Piehler","sequence":"additional","affiliation":[{"name":"Institute of Immunology\/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig 1 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Grahnert","sequence":"additional","affiliation":[{"name":"Institute of Immunology\/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig 1 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Protschka","sequence":"additional","affiliation":[{"name":"Institute of Immunology\/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig 1 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Gerhard-Domagk-Institute of Pathology, University of M\u00fcnster 3 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Frey","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Jena 4 , Jena , Germany"},{"name":"Institute of Clinical Chemistry and Laboratory Diagnostics 6 Present address: , University Hospital Jena, Jena , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephin","family":"Held","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin 2 , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Richter","sequence":"additional","affiliation":[{"name":"Institute of Immunology\/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig 1 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Eschke","sequence":"additional","affiliation":[{"name":"Institute of Immunology\/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig 1 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kamradt","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Jena 4 , Jena , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Brombacher","sequence":"additional","affiliation":[{"name":"International Center for Genetic Engineering and Biotechnology (ICGEB) and Institute of Infectious Diseases and Molecular Medicine (IIDMM), University of Cape Town 5 , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gottfried","family":"Alber","sequence":"additional","affiliation":[{"name":"Institute of Immunology\/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig 1 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,3,26]]},"reference":[{"key":"2022073001193261700_CIT0001","doi-asserted-by":"crossref","first-page":"4345","DOI":"10.1128\/IAI.00542-09","article-title":"Spores as infectious propagules of Cryptococcus neoformans","volume":"77","author":"Velagapudi","year":"2009","journal-title":"Infect. 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