{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:47:44Z","timestamp":1791308864402,"version":"4.3.1"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,5,10]]},"abstract":"<jats:p>Patients taking immunosuppressive drugs, like cyclosporine A (CsA), that inhibit calcineurin are highly susceptible to disseminated fungal infections, although it is unclear how these drugs suppress resistance to these opportunistic pathogens. We show that in a mouse model of disseminated Candida albicans infection, CsA-induced susceptibility to fungal infection maps to the innate immune system. To further define the cell types targeted by CsA, we generated mice with a conditional deletion of calcineurin B (CnB) in neutrophils. These mice displayed markedly decreased resistance to infection with C. albicans, and both CnB-deficient and CsA-treated neutrophils showed a defect in the ex vivo killing of C. albicans. In response to the fungal-derived pathogen-associated molecular pattern zymosan, neutrophils lacking CnB displayed impaired up-regulation of genes (IL-10, Cox2, Egr1, and Egr2) regulated by nuclear factor of activated T cells, the best characterized CnB substrate. This activity was Myd88 independent and was reproduced by stimulation with the \u03b2(1,3) glucan curdlan, indicating that dectin-1, rather than toll-like receptors, is the upstream activator of calcineurin. Our results suggest that disseminated fungal infections seen in CsA-treated patients are not just a general consequence of systemic suppression of adaptive immunity but are, rather, a result of the specific blockade of evolutionarily conserved innate pathways for fungal resistance.<\/jats:p>","DOI":"10.1084\/jem.20092531","type":"journal-article","created":{"date-parts":[[2010,4,26]],"date-time":"2010-04-26T22:18:47Z","timestamp":1272320327000},"page":"923-931","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":140,"title":["Calcineurin regulates innate antifungal immunity in neutrophils"],"prefix":"10.1084","volume":"207","author":[{"given":"Matthew B.","family":"Greenblatt","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health 1 , and 2 and 3"},{"name":"Department of Medicine 1 , and 2 and 3"},{"name":"Division of Rheumatology, Allergy and Immunology, Brigham and Women\u2019s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115 1 , and 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios","family":"Aliprantis","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health 1 , and 2 and 3"},{"name":"Department of Medicine 1 , and 2 and 3"},{"name":"Division of Rheumatology, Allergy and Immunology, Brigham and Women\u2019s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115 1 , and 2 and 3"},{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health 1 , and 2 and 3"},{"name":"Department of Medicine 1 , and 2 and 3"},{"name":"Division of Rheumatology, Allergy and Immunology, Brigham and Women\u2019s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115 1 , and 2 and 3"},{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health 1 , and 2 and 3"},{"name":"Department of Medicine 1 , and 2 and 3"},{"name":"Division of Rheumatology, Allergy and Immunology, Brigham and Women\u2019s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115 1 , and 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health 1 , and 2 and 3"},{"name":"Department of Medicine 1 , and 2 and 3"},{"name":"Division of Rheumatology, Allergy and Immunology, Brigham and Women\u2019s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115 1 , and 2 and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie H.","family":"Glimcher","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health 1 , and 2 and 3"},{"name":"Department of Medicine 1 , and 2 and 3"},{"name":"Division of Rheumatology, Allergy and Immunology, Brigham and Women\u2019s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115 1 , and 2 and 3"},{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health 1 , and 2 and 3"},{"name":"Department of Medicine 1 , and 2 and 3"},{"name":"Division of Rheumatology, Allergy and Immunology, Brigham and Women\u2019s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115 1 , and 2 and 3"},{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health 1 , and 2 and 3"},{"name":"Department of Medicine 1 , and 2 and 3"},{"name":"Division of Rheumatology, Allergy and Immunology, Brigham and Women\u2019s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115 1 , and 2 and 3"},{"name":"Ragon Institute of Massachusetts General Hospital, Harvard and MIT, Charlestown, MA 02129 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2010,4,26]]},"reference":[{"key":"2023072601374630200_bib1","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.1172\/JCI35711","article-title":"NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism","volume":"118","author":"Aliprantis","year":"2008","journal-title":"J. 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