{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:26:02Z","timestamp":1791419162007,"version":"4.3.3"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"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":[[2014,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Oropharyngeal candidiasis (OPC), caused by the commensal fungus Candida albicans, is an opportunistic infection associated with infancy, AIDS, and IL-17\u2013related primary immunodeficiencies. The Th17-associated cytokines IL-23 and IL-17 are crucial for immunity to OPC, but the mechanisms by which they mediate immunity are poorly defined. IL-17RA\u2013deficient humans and mice are strongly susceptible to OPC, with reduced levels of CXC chemokines and concomitantly impaired neutrophil recruitment to the oral mucosa. Paradoxically, humans with isolated neutropenia are typically not susceptible to candidiasis. To determine whether immunity to OPC is mediated via neutrophil recruitment, mice lacking CXCR2 were subjected to OPC and were found to be highly susceptible, although there was no dissemination of fungi to peripheral organs. To assess whether the entire neutrophil response is IL-17 dependent, IL-17RA\u2212\/\u2212 and IL-23\u2212\/\u2212 mice were administered neutrophil-depleting Abs and subjected to OPC. These mice displayed increased oral fungal burdens compared with IL-17RA\u2212\/\u2212 or IL-23\u2212\/\u2212 mice alone, indicating that additional IL-17\u2013independent signals contribute to the neutrophil response. WT mice treated with anti\u2013Gr-1 Abs exhibited a robust infiltrate of CD11b+Ly-6GlowF4\/80\u2212 cells to the oral mucosa but were nonetheless highly susceptible to OPC, indicating that this monocytic influx is insufficient for host defense. Surprisingly, Ly-6G Ab treatment did not induce the same strong susceptibility to OPC in WT mice. Thus, CXCR2+ and Gr-1+ neutrophils play a vital role in host defense against OPC. Moreover, defects in the IL-23\/17 axis cause a potent but incomplete deficiency in the neutrophil response to oral candidiasis.<\/jats:p>","DOI":"10.4049\/jimmunol.1302265","type":"journal-article","created":{"date-parts":[[2014,1,18]],"date-time":"2014-01-18T06:12:02Z","timestamp":1390025522000},"page":"1745-1752","source":"Crossref","is-referenced-by-count":122,"title":["Role of Neutrophils in IL-17\u2013Dependent Immunity to Mucosal Candidiasis"],"prefix":"10.1093","volume":"192","author":[{"given":"Anna R","family":"Huppler","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of UPMC , Pittsburgh, PA 15224"},{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather R","family":"Conti","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nydiaris","family":"Hern\u00e1ndez-Santos","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Darville","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of UPMC , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha S","family":"Biswas","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L","family":"Gaffen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,15]]},"reference":[{"key":"2025032404134565700_r1","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s00431-007-0527-7","article-title":"Fungal infections in primary immunodeficiencies","volume":"166","author":"Antachopoulos","year":"2007","journal-title":"Eur. J. Pediatr."},{"key":"2025032404134565700_r2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1834-7819.2010.01198.x","article-title":"Oral fungal infections: an update for the general practitioner","volume":"55","author":"Farah","year":"2010","journal-title":"Aust. Dent. J."},{"key":"2025032404134565700_r3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/ar3893","article-title":"Mucocutaneous candidiasis: the IL-17 pathway and implications for targeted immunotherapy","volume":"14","author":"Huppler","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"2025032404134565700_r4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1084\/jem.20081463","article-title":"Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis","volume":"206","author":"Conti","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032404134565700_r5","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nature06764","article-title":"Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome","volume":"452","author":"Milner","year":"2008","journal-title":"Nature"},{"key":"2025032404134565700_r6","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s12026-011-8226-x","article-title":"IL-17 signaling in host defense against Candida albicans","volume":"50","author":"Gaffen","year":"2011","journal-title":"Immunol. Res."},{"key":"2025032404134565700_r7","doi-asserted-by":"crossref","first-page":"776","DOI":"10.5483\/BMBRep.2009.42.12.776","article-title":"Th17 responses and host defense against microorganisms: an overview","volume":"42","author":"van de Veerdonk","year":"2009","journal-title":"BMB Rep."},{"key":"2025032404134565700_r8","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1084\/jem.194.4.519","article-title":"Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense","volume":"194","author":"Ye","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025032404134565700_r9","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.4049\/jimmunol.0903739","article-title":"IL-17RC is required for immune signaling via an extended SEF\/IL-17R signaling domain in the cytoplasmic tail","volume":"185","author":"Ho","year":"2010","journal-title":"J. Immunol."},{"key":"2025032404134565700_r10","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.2041-1014.2010.00570.x","article-title":"Early activation of the interleukin-23-17 axis in a murine model of oropharyngeal candidiasis","volume":"25","author":"Saunus","year":"2010","journal-title":"Mol Oral Microbiol."},{"key":"2025032404134565700_r11","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1126\/science.1200439","article-title":"Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity","volume":"332","author":"Puel","year":"2011","journal-title":"Science"},{"key":"2025032404134565700_r12","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.immuni.2013.09.002","article-title":"An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis","volume":"39","author":"Boisson","year":"2013","journal-title":"Immunity"},{"key":"2025032404134565700_r13","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1371\/journal.ppat.0040035","article-title":"Mucosal damage and neutropenia are required for Candida albicans dissemination","volume":"4","author":"Koh","year":"2008","journal-title":"PLoS Pathog."},{"key":"2025032404134565700_r14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.2165\/11315500-000000000-00000","article-title":"Epidemiology, incidence and risk factors for invasive candidiasis in high-risk patients","volume":"69","author":"Concia","year":"2009","journal-title":"Drugs"},{"key":"2025032404134565700_r15","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0924-8579(00)00218-1","article-title":"Management of fungal infections in neutropenic patients: more doubts than certainties?","volume":"16","author":"Del Favero","year":"2000","journal-title":"Int. J. Antimicrob. Agents"},{"key":"2025032404134565700_r16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1053\/j.seminhematol.2006.04.004","article-title":"Severe congenital neutropenia","volume":"43","author":"Welte","year":"2006","journal-title":"Semin. Hematol."},{"key":"2025032404134565700_r17","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1007\/s001090050267","article-title":"Clinical manifestation of myeloperoxidase deficiency","volume":"76","author":"Lanza","year":"1998","journal-title":"J. Mol. Med. (Berl)."},{"key":"2025032404134565700_r18","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1146\/annurev.immunol.22.012703.104543","article-title":"Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells","volume":"22","author":"Rot","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"2025032404134565700_r19","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1126\/science.8036519","article-title":"Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog","volume":"265","author":"Cacalano","year":"1994","journal-title":"Science"},{"key":"2025032404134565700_r20","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1172\/JCI27009","article-title":"Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung","volume":"116","author":"Reutershan","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025032404134565700_r21","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1152\/ajpregu.00738.2001","article-title":"Chemokines and chemokine receptors in leukocyte trafficking","volume":"283","author":"Olson","year":"2002","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2025032404134565700_r22","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1172\/JCI60588","article-title":"Cxcr2 and Cxcl5 regulate the IL-17\/G-CSF axis and neutrophil homeostasis in mice","volume":"122","author":"Mei","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2025032404134565700_r23","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1006\/cyto.1998.0465","article-title":"Cxc chemokine receptor expression on human endothelial cells","volume":"11","author":"Murdoch","year":"1999","journal-title":"Cytokine"},{"key":"2025032404134565700_r24","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1128\/IAI.05535-11","article-title":"Enhanced neutrophil longevity and recruitment contribute to the severity of oviduct pathology during Chlamydia muridarum infection","volume":"79","author":"Frazer","year":"2011","journal-title":"Infect. Immun."},{"key":"2025032404134565700_r25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1471-2172-13-65","article-title":"Depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased IL-17A production by \u03b3\u03b4 T cells","volume":"13","author":"Wozniak","year":"2012","journal-title":"BMC Immunol."},{"key":"2025032404134565700_r26","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.4049\/jimmunol.163.11.6086","article-title":"CXC chemokine receptor-2 ligands are necessary components of neutrophil-mediated host defense in invasive pulmonary aspergillosis","volume":"163","author":"Mehrad","year":"1999","journal-title":"J. Immunol."},{"key":"2025032404134565700_r27","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1189\/jlb.0407247","article-title":"Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice","volume":"83","author":"Daley","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"2025032404134565700_r28","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1128\/AAC.45.11.3195-3197.2001","article-title":"New model of oropharyngeal candidiasis in mice","volume":"45","author":"Kamai","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"2025032404134565700_r29","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1172\/JCI41649","article-title":"CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow","volume":"120","author":"Eash","year":"2010","journal-title":"J. Clin. Invest."},{"key":"2025032404134565700_r30","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cyto.2007.11.013","article-title":"Structure-function relationships in the IL-17 receptor: implications for signal transduction and therapy","volume":"41","author":"Shen","year":"2008","journal-title":"Cytokine"},{"key":"2025032404134565700_r31","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1182\/blood-2005-09-010116","article-title":"An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor-dependent signals","volume":"109","author":"Yu","year":"2007","journal-title":"Blood"},{"key":"2025032404134565700_r32","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.immuni.2009.08.001","article-title":"Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity","volume":"31","author":"Sutton","year":"2009","journal-title":"Immunity"},{"key":"2025032404134565700_r33","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.smim.2007.10.016","article-title":"Targeting the development and effector functions of TH17 cells","volume":"19","author":"Ghilardi","year":"2007","journal-title":"Semin. Immunol."},{"key":"2025032404134565700_r34","doi-asserted-by":"crossref","first-page":"6337","DOI":"10.1158\/0008-5472.CAN-04-0757","article-title":"High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells","volume":"64","author":"Serafini","year":"2004","journal-title":"Cancer Res."},{"key":"2025032404134565700_r35","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1182\/blood.V96.12.3838","article-title":"Identification of a CD11b(+)\/Gr-1(+)\/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells","volume":"96","author":"Bronte","year":"2000","journal-title":"Blood"},{"key":"2025032404134565700_r36","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.4049\/jimmunol.169.6.3180","article-title":"CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis","volume":"169","author":"Mencacci","year":"2002","journal-title":"J. Immunol."},{"key":"2025032404134565700_r37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fimmu.2012.00263","article-title":"CXCR2: from bench to bedside","volume":"3","author":"Stadtmann","year":"2012","journal-title":"Front. Immunol."},{"key":"2025032404134565700_r38","doi-asserted-by":"crossref","first-page":"6528","DOI":"10.1128\/IAI.00909-06","article-title":"Early neutrophil recruitment and aggregation in the murine lung inhibit germination of Aspergillus fumigatus Conidia","volume":"74","author":"Bonnett","year":"2006","journal-title":"Infect. Immun."},{"key":"2025032404134565700_r39","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.4049\/jimmunol.168.3.1447","article-title":"CXCR2 is necessary for the development and persistence of chronic fungal asthma in mice","volume":"168","author":"Schuh","year":"2002","journal-title":"J. Immunol."},{"key":"2025032404134565700_r40","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":"2025032404134565700_r41","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1189\/jlb.0213063","article-title":"Candida albicans escapes from mouse neutrophils","volume":"94","author":"Ermert","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"2025032404134565700_r42","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/mi.2011.5","article-title":"New mechanism of oral immunity to mucosal candidiasis in hyper-IgE syndrome","volume":"4","author":"Conti","year":"2011","journal-title":"Mucosal Immunol."},{"key":"2025032404134565700_r43","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.smim.2007.10.009","article-title":"Th17 cells and mucosal host defense","volume":"19","author":"Aujla","year":"2007","journal-title":"Semin. Immunol."},{"key":"2025032404134565700_r44","doi-asserted-by":"crossref","first-page":"6110","DOI":"10.1128\/IAI.69.10.6110-6118.2001","article-title":"T cells augment monocyte and neutrophil function in host resistance against oropharyngeal candidiasis","volume":"69","author":"Farah","year":"2001","journal-title":"Infect. Immun."},{"key":"2025032404134565700_r45","first-page":"500","article-title":"Severe congenital neutropenia in 2 siblings of consanguineous parents. The role of HAX1 deficiency","volume":"19","author":"Mamishi","year":"2009","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"2025032404134565700_r46","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1056\/NEJMoa1109997","article-title":"Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis","volume":"366","author":"Leonardi","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2025032404134565700_r47","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1056\/NEJMoa1109017","article-title":"Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis","volume":"366","author":"Papp","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2025032404134565700_r48","doi-asserted-by":"crossref","first-page":"ii116","DOI":"10.1136\/annrheumdis-2012-202371","article-title":"Effect of IL-17A blockade with secukinumab in autoimmune diseases","volume":"72","author":"Patel","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"2025032404134565700_r49","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1038\/ajg.2013.138","article-title":"Opportunistic infections with anti-tumor necrosis factor-\u03b1 therapy in inflammatory bowel disease: meta-analysis of randomized controlled trials","volume":"108","author":"Ford","year":"2013","journal-title":"Am. J. Gastroenterol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/4\/1745\/62509667\/1302265.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/4\/1745\/62509667\/1302265.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T06:06:24Z","timestamp":1742796384000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/192\/4\/1745\/7996654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,2,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1302265","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,2]]},"published":{"date-parts":[[2014,2]]}}}