{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:45Z","timestamp":1787030865702,"version":"build-2736575974"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020M33A9D30378911"],"award-info":[{"award-number":["NRF-2020M33A9D30378911"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A5A2021242"],"award-info":[{"award-number":["2018R1A5A2021242"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Invasive candidiasis has high mortality rates in immunocompromised patients, causing serious health problems. In mouse models, innate immunity protects the host by rapidly mobilizing a variety of resistance and tolerance mechanisms to systemic Candida albicans infection. We have previously demonstrated that exogenous IL-33 regulates multiple steps of innate immunity involving resistance and tolerance processes. In this study, we systematically analyzed the in vivo functions of endogenous IL-33 using Il33\u2212\/\u2212 mice and in vitro immune cell culture. Tubular epithelial cells mainly secreted IL-33 in response to systemic C. albicans infection. Il33\u2212\/\u2212 mice showed increased mortality and morbidity, which were due to impaired fungal clearance. IL-33 initiated an innate defense mechanism by costimulating dendritic cells to produce IL-23 after systemic C. albicans infection, which in turn promoted the phagocytosis of neutrophils through secretion of GM-CSF by NK cells. The susceptibility of Il33\u2212\/\u2212 mice was also associated with increased levels of IL-10, and neutralization of IL-10 resulted in enhanced fungal clearance in Il33\u2212\/\u2212 mice. However, depletion of IL-10 overrode the effect of IL-33 on fungal clearance. In Il10\u2212\/\u2212 mouse kidneys, MHC class II+F4\/80+ macrophages were massively differentiated after C. albicans infection, and these cells were superior to MHC class II\u2212F4\/80+ macrophages that were preferentially differentiated in wild-type mouse kidneys in killing of extracellular hyphal C. albicans. Taken together, our results identify IL-33 as critical early regulator controlling a serial downstream signaling events of innate defense to C. albicans infection.<\/jats:p>","DOI":"10.4049\/jimmunol.2100495","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T09:20:14Z","timestamp":1641979214000},"page":"660-671","source":"Crossref","is-referenced-by-count":8,"title":["IL-33 Coordinates Innate Defense to Systemic\n                    <i>Candida albicans<\/i>\n                    Infection by Regulating IL-23 and IL-10 in an Opposite Way"],"prefix":"10.1093","volume":"208","author":[{"given":"Nu Z N","family":"Nguyen","sequence":"first","affiliation":[{"name":"BK21 Integrated Immunomodulation Education and Research Team, School of Biological Sciences, University of Ulsan , Ulsan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0993-1672","authenticated-orcid":false,"given":"Vuvi G","family":"Tran","sequence":"additional","affiliation":[{"name":"Center for Immunology and Infectious Diseases, University of California at Davis , Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyeon","family":"Baek","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan , Ulsan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younghee","family":"Kim","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan , Ulsan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5673-2417","authenticated-orcid":false,"given":"Eun H","family":"Youn","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, Inje University , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung W","family":"Na","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan , Ulsan,","place":["Republic of Korea"]},{"name":"Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, School of Medicine, University of Ulsan , Ulsan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8112-6331","authenticated-orcid":false,"given":"Sang J","family":"Park","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan , Ulsan,","place":["Republic of Korea"]},{"name":"Department of Surgery, Ulsan University Hospital, School of Medicine, University of Ulsan , Ulsan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Kil","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, Inje University , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8575-0115","authenticated-orcid":false,"given":"Byungsuk","family":"Kwon","sequence":"additional","affiliation":[{"name":"BK21 Integrated Immunomodulation Education and Research Team, School of Biological Sciences, University of Ulsan , Ulsan,","place":["Republic of Korea"]},{"name":"Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan , Ulsan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,1]]},"reference":[{"key":"2025021008532078000_r1","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1086\/320757","article-title":"Risk factors and predictors of outcome in patients with cancer and breakthrough candidemia","volume":"32","author":"Uzun","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"2025021008532078000_r2","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1086\/599039","article-title":"Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry","volume":"48","author":"Horn","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"2025021008532078000_r3","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1099\/13500872-142-12-3487","article-title":"Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis in mice, and reveals differences between brain and kidney in mechanisms of host resistance","volume":"142","author":"Fulurija","year":"1996","journal-title":"Microbiology (Reading)"},{"key":"2025021008532078000_r4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/infdis\/jit413","article-title":"Inflammatory monocytes mediate early and organ-specific innate defense during systemic candidiasis","volume":"209","author":"Ngo","year":"2014","journal-title":"J. Infect. Dis."},{"key":"2025021008532078000_r5","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1172\/JCI71307","article-title":"CX3CR1-dependent renal macrophage survival promotes Candida control and host survival","volume":"123","author":"Lionakis","year":"2013","journal-title":"J. Clin. Invest."},{"key":"2025021008532078000_r6","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1086\/527390","article-title":"Adjuvant corticosteroid therapy for chronic disseminated candidiasis","volume":"46","author":"Legrand","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"2025021008532078000_r7","doi-asserted-by":"crossref","first-page":"e1002811","DOI":"10.1371\/journal.ppat.1002811","article-title":"Type I interferons promote fatal immunopathology by regulating inflammatory monocytes and neutrophils during Candida infections","volume":"8","author":"Majer","year":"2012","journal-title":"PLoS Pathog."},{"key":"2025021008532078000_r8","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.immuni.2017.05.009","article-title":"Inflammatory Ly6Chigh monocytes protect against Candidiasis through IL-15-driven NK cell\/neutrophil activation","volume":"46","author":"Dom\u00ednguez-Andr\u00e9s","year":"2017","journal-title":"Immunity"},{"key":"2025021008532078000_r9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.immuni.2013.12.002","article-title":"IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells","volume":"40","author":"B\u00e4r","year":"2014","journal-title":"Immunity"},{"key":"2025021008532078000_r10","doi-asserted-by":"crossref","first-page":"e1004276","DOI":"10.1371\/journal.ppat.1004276","article-title":"Syk signaling in dendritic cells orchestrates innate resistance to systemic fungal infection [Published erratum appears in 2018 PLoS Pathog. 14: e1007366.]","volume":"10","author":"Whitney","year":"2014","journal-title":"PLoS Pathog."},{"key":"2025021008532078000_r11","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.4110\/in.2020.20.e49","article-title":"CCR5-mediated recruitment of NK cells to the kidney is a critical step for host defense to systemic Candida albicans infection","volume":"20","author":"Nguyen","year":"2020","journal-title":"Immune Netw."},{"key":"2025021008532078000_r12","doi-asserted-by":"crossref","first-page":"e20190418","DOI":"10.1084\/jem.20190418","article-title":"Biology and therapeutic potential of interleukin-10","volume":"217","author":"Saraiva","year":"2020","journal-title":"J. Exp. Med."},{"key":"2025021008532078000_r13","doi-asserted-by":"crossref","first-page":"3712","DOI":"10.4049\/jimmunol.172.6.3712","article-title":"Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells","volume":"172","author":"Netea","year":"2004","journal-title":"J. Immunol."},{"key":"2025021008532078000_r14","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1172\/JCI25439","article-title":"Toll-like receptor 2 controls expansion and function of regulatory T cells","volume":"116","author":"Sutmuller","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025021008532078000_r15","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nri.2016.95","article-title":"Interleukin-33 in health and disease","volume":"16","author":"Liew","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"2025021008532078000_r16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.4049\/jimmunol.1103564","article-title":"IL-33 priming regulates multiple steps of the neutrophil-mediated anti-Candida albicans response by modulating TLR and dectin-1 signals","volume":"189","author":"Le","year":"2012","journal-title":"J. Immunol."},{"key":"2025021008532078000_r17","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.4049\/jimmunol.1402986","article-title":"IL-33 enhances host tolerance to Candida albicans kidney infections through induction of IL-13 production by CD4+ T cells","volume":"194","author":"Tran","year":"2015","journal-title":"J. Immunol."},{"key":"2025021008532078000_r18","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.celrep.2019.06.020","article-title":"EphA2 is a neutrophil receptor for Candida albicans that stimulates antifungal activity during oropharyngeal infection","volume":"28","author":"Swidergall","year":"2019","journal-title":"Cell Rep."},{"key":"2025021008532078000_r19","first-page":"E13","article-title":"Reverse signaling through the costimulatory ligand CD137L in epithelial cells is essential for natural killer cell-mediated acute tissue inflammation","volume":"109","author":"Kim","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008532078000_r20","doi-asserted-by":"crossref","first-page":"e1008115","DOI":"10.1371\/journal.ppat.1008115","article-title":"IL-23 supports host defense against systemic Candida albicans infection by ensuring myeloid cell survival","volume":"15","author":"Nur","year":"2019","journal-title":"PLoS Pathog."},{"key":"2025021008532078000_r21","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.coi.2014.09.004","article-title":"IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy","volume":"31","author":"Cayrol","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"2025021008532078000_r22","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.jaci.2009.02.026","article-title":"IL-33-activated dendritic cells induce an atypical TH2-type response","volume":"123","author":"Rank","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025021008532078000_r23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cyto.2017.07.022","article-title":"IL-33-matured dendritic cells promote Th17 cell responses via IL-1\u03b2 and IL-6","volume":"99","author":"Park","year":"2017","journal-title":"Cytokine"},{"key":"2025021008532078000_r24","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.imlet.2019.12.003","article-title":"IL-33 changes CD25hi Tregs to Th17 cells through a dendritic cell-mediated pathway","volume":"218","author":"Park","year":"2020","journal-title":"Immunol. Lett."},{"key":"2025021008532078000_r25","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1128\/IAI.68.4.2363-2365.2000","article-title":"Disparate requirement for T cells in resistance to mucosal and acute systemic candidiasis","volume":"68","author":"Jones-Carson","year":"2000","journal-title":"Infect. Immun."},{"key":"2025021008532078000_r26","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.4049\/jimmunol.1401675","article-title":"Cutting edge: Failure of antigen-specific CD4+ T cell recruitment to the kidney during systemic candidiasis","volume":"193","author":"Drummond","year":"2014","journal-title":"J. Immunol."},{"key":"2025021008532078000_r27","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41581-019-0110-2","article-title":"Macrophages: versatile players in renal inflammation and fibrosis","volume":"15","author":"Tang","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"2025021008532078000_r28","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.immuni.2014.03.011","article-title":"Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function","volume":"40","author":"Shouval","year":"2014","journal-title":"Immunity"},{"key":"2025021008532078000_r29","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.immuni.2014.03.012","article-title":"Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis","volume":"40","author":"Zigmond","year":"2014","journal-title":"Immunity"},{"key":"2025021008532078000_r30","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1126\/science.1235208","article-title":"Blockade of chronic type I interferon signaling to control persistent LCMV infection","volume":"340","author":"Wilson","year":"2013","journal-title":"Science"},{"key":"2025021008532078000_r31","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1126\/science.1235214","article-title":"Persistent LCMV infection is controlled by blockade of type I interferon signaling","volume":"340","author":"Teijaro","year":"2013","journal-title":"Science"},{"key":"2025021008532078000_r32","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.immuni.2013.05.010","article-title":"Interferon-\u03b2 production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans","volume":"38","author":"del Fresno","year":"2013","journal-title":"Immunity"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/3\/660\/61466130\/ji2100495.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/3\/660\/61466130\/ji2100495.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T03:53:34Z","timestamp":1739159614000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/208\/3\/660\/7924591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,1]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,2,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2100495","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2]]},"published":{"date-parts":[[2022,2,1]]}}}