{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:47:59Z","timestamp":1787611679883,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We investigated the effect of human beta defensin-2 (hBD-2) on nasal epithelial barrier function with methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) infection in chronic rhinosinusitis with nasal polyps (CRSwNP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of hBD-2 was measured in nasal polyps (NPs) from CRSwNP. MRSA was treated with different concentrations of hBD-2 to assess the invasive ability. Primary human nasal epithelial cells (HNECs) cultured at the air\u2013liquid interface (ALI) were pre-incubated with or without hBD-2 prior to MRSA infection. The cell viability, the epithelial cell integrity, and the tight junction (TJ) expression were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of hBD-2 in the CRSwNP group was higher than that in the control group. In addition, the hBD-2 protein was negatively correlated with the Lund\u2013Mackay CT score and was positively correlated with the neutrophil levels in CRSwNP. The presence of hBD-2 significantly reduced the invasive ability of MRSA in HNECs. MRSA decreased the epithelial cell integrity by diminishing the protein expression of occludin and zonula occludens-1 (ZO-1). Furthermore, hBD-2 prevented the MRSA-induced barrier disruption by increasing the mucosal permeability and the expression of occludin and ZO-1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results suggest that hBD-2 may partially attenuate the epithelial barrier disruption induced by MRSA, indicating the protective effect of hBD-2 on <jats:italic>S. aureus<\/jats:italic> infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1551080","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T05:37:35Z","timestamp":1746769055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Human beta defensin-2 protects the epithelial barrier during methicillin-resistant Staphylococcus aureus infection in chronic rhinosinusitis with nasal polyps"],"prefix":"10.3389","volume":"15","author":[{"given":"Tengfei","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szuyao","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianyang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunquan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/MOO.0000000000000324","article-title":"Sinonasal methicillin-resistant staphylococcus aureus: updates on treatment","volume":"25","author":"Al-Asousi","year":"2017","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"B2","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.jaci.2018.01.046","article-title":"Staphylococcus aureus enhances the tight junction barrier integrity in healthy nasal tissue, but not in nasal polyps","volume":"142","author":"Altunbulakli","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41572-020-00218-1","article-title":"Adult chronic rhinosinusitis","volume":"6","author":"Bachert","year":"2020","journal-title":"Nat. Rev. Dis. Prime."},{"key":"B4","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.ceb.2016.05.006","article-title":"Tight junctions as regulators of tissue remodelling","volume":"42","author":"Balda","year":"2016","journal-title":"Curr. Opin. Cell. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/alr.21546","article-title":"Remodeling changes of the upper airway with chronic rhinosinusitis","volume":"5","author":"Barham","year":"2015","journal-title":"Int. Forum Allergy Rhinol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0609382","article-title":"Human defensins and LL-37 in mucosal immunity","volume":"87","author":"Doss","year":"2010","journal-title":"J. Leukoc. Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.636061","article-title":"Human beta-defensin 2 mutations are associated with asthma and atopy in children and its application prevents atopic asthma in a mouse model","volume":"12","author":"Borchers","year":"2021","journal-title":"Front. Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.2500\/105065801779954238","article-title":"Production of beta-defensin antimicrobial peptides by maxillary sinus mucosa","volume":"15","author":"Carothers","year":"2001","journal-title":"Am. J. Rhinol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.jmii.2016.12.005","article-title":"Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria","volume":"50","author":"Chung","year":"2017","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cells10112991","article-title":"Human beta-defensin 2 and its postulated role in modulation of the immune response","volume":"10","author":"Cieslik","year":"2021","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1034\/j.1398-9995.2003.00180.x","article-title":"Human beta-defensins and toll-like receptors in the upper airway","volume":"58","author":"Claeys","year":"2003","journal-title":"Allergy"},{"key":"B12","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3390\/pathogens2010177","article-title":"Antimicrobial human beta-defensins in the colon and their role in infectious and non-infectious diseases","volume":"2","author":"Cobo","year":"2013","journal-title":"Pathogens"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00057","article-title":"Chronic rhinosinusitis: potential role of microbial dysbiosis and recommendations for sampling sites","volume":"8","author":"Copeland","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1128\/CMR.13.1.16","article-title":"Exotoxins of staphylococcus aureus","volume":"13","author":"Dinges","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4193\/Rhin20.600","article-title":"European position paper on rhinosinusitis and nasal polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s11882-012-0246-7","article-title":"Role of bacterial and fungal biofilms in chronic rhinosinusitis","volume":"12","author":"Foreman","year":"2012","journal-title":"Curr. Allergy Asthma Rep."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.666900","article-title":"Antimicrobial peptides human beta-defensin-2 and -3 protect the gut during candida albicans infections enhancing the intestinal barrier integrity: in vitro study","volume":"11","author":"Fusco","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1016\/j.jaci.2020.04.010","article-title":"Epithelial barriers in allergy and asthma","volume":"145","author":"Hellings","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1007\/s00405-015-3816-1","article-title":"Different activations of toll-like receptors and antimicrobial peptides in chronic rhinosinusitis with or without nasal polyposis","volume":"273","author":"Hirschberg","year":"2016","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s00405-002-0500-z","article-title":"Localization of ZO-1 and e-cadherin in the nasal polyp epithelium","volume":"259","author":"Jang","year":"2002","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"549","DOI":"10.2500\/ajra.2009.23.3366","article-title":"Impaired mucosal healing and infection associated with staphylococcus aureus after endoscopic sinus surgery","volume":"23","author":"Jervis-Bardy","year":"2009","journal-title":"Am. J. Rhinol. Allergy"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1038\/jid.2014.143","article-title":"Host defense (antimicrobial) peptide, human beta-defensin-3, improves the function of the epithelial tight-junction barrier in human keratinocytes","volume":"134","author":"Kiatsurayanon","year":"2014","journal-title":"J. Invest. Dermatol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1177\/000348940211100205","article-title":"Antimicrobial defensin peptides of the human nasal mucosa","volume":"111","author":"Lee","year":"2002","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1016\/j.jaci.2022.11.031","article-title":"Alterations of nasal microbiome in eosinophilic chronic rhinosinusitis","volume":"151","author":"Liang","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1016\/S0194-59989770005-6","article-title":"Staging for rhinosinusitis","volume":"117","author":"Lund","year":"1997","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111401","article-title":"Mechanism of antimicrobial peptides: antimicrobial, anti-inflammatory and antibiofilm activities","volume":"22","author":"Luo","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-6-116","article-title":"Respiratory epithelial cells require toll-like receptor 4 for induction of human beta-defensin 2 by lipopolysaccharide","volume":"6","author":"MacRedmond","year":"2005","journal-title":"Respir. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1002\/alr.21517","article-title":"Staphylococcus aureus impairs the airway epithelial barrier in vitro. Int","volume":"5","author":"Malik","year":"2015","journal-title":"Forum Allergy Rhinol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1111\/all.13532","article-title":"Mucosal zinc deficiency in chronic rhinosinusitis with nasal polyposis contributes to barrier disruption and decreases ZO-1","volume":"73","author":"Murphy","year":"2018","journal-title":"Allergy"},{"key":"B30","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1615\/critrevimmunol.v26.i6.60","article-title":"Human defensins and cathelicidins in the skin: beyond direct antimicrobial properties","volume":"26","author":"Niyonsaba","year":"2006","journal-title":"Crit. Rev. Immunol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.663626","article-title":"Nasal epithelial barrier integrity and tight junctions disruption in allergic rhinitis: overview and pathogenic insights","volume":"12","author":"Nur","year":"2021","journal-title":"Front. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.jaci.2015.01.043","article-title":"Oncostatin m promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease","volume":"136","author":"Pothoven","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"115","DOI":"10.2500\/ajr.2008.22.3136","article-title":"Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells","volume":"22","author":"Ramanathan","year":"2008","journal-title":"Am. J. Rhinol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1002\/alr.20014","article-title":"Epithelial tight junction alterations in nasal polyposis","volume":"1","author":"Rogers","year":"2011","journal-title":"Int. Forum Allergy Rhinol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1016\/j.jaci.2007.08.046","article-title":"Epithelium: at the interface of innate and adaptive immune responses","volume":"120","author":"Schleimer","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1007\/s00109-005-0657-1","article-title":"Human defensins","volume":"83","author":"Schneider","year":"2005","journal-title":"J. Mol. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1016\/j.jaip.2022.01.016","article-title":"Epidemiology of chronic rhinosinusitis: prevalence and risk factors","volume":"10","author":"Sedaghat","year":"2022","journal-title":"J. Allergy Clin. Immunol.-Pract."},{"key":"B38","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/all.12577","article-title":"Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities","volume":"70","author":"Shi","year":"2015","journal-title":"Allergy"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-10-36","article-title":"The expression of the beta-defensins hBD-2 and hBD-3 is differentially regulated by NF-kappab and MAPK\/AP-1 pathways in an in vitro model of candida esophagitis","volume":"10","author":"Steubesand","year":"2009","journal-title":"BMC Immunol."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2016.1251384","article-title":"Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases","volume":"4","author":"Sturgeon","year":"2016","journal-title":"Tissue Barriers."},{"key":"B41","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.burns.2004.03.012","article-title":"Expression of human beta-defensins HBD-1, HBD-2, and HBD-3 in cultured keratinocytes and skin substitutes","volume":"30","author":"Supp","year":"2004","journal-title":"Burns"},{"key":"B42","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/nrmicro3521","article-title":"Staphylococcal manipulation of host immune responses","volume":"13","author":"Thammavongsa","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s11882-019-0853-7","article-title":"The role of staphylococcus aureus in patients with chronic sinusitis and nasal polyposis","volume":"19","author":"Vickery","year":"2019","journal-title":"Curr. Allergy Asthma Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jid.2016.08.025","article-title":"IL-1beta-induced protection of keratinocytes against staphylococcus aureus-secreted proteases is mediated by human beta-defensin 2","volume":"137","author":"Wang","year":"2017","journal-title":"J. Invest. Dermatol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1551080\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T05:37:37Z","timestamp":1746769057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1551080\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,9]]},"references-count":44,"alternative-id":["10.3389\/fcimb.2025.1551080"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1551080","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,9]]},"article-number":"1551080"}}