{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:39:51Z","timestamp":1776771591945,"version":"3.51.2"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Chitin, a polysaccharide, is ubiquitously found in nature and has been known to be an active immunogen in mammals, and interacts with Toll-like, mannose and glucan receptors, to induce cytokine and chemokine secretions. FIBCD1 is a tetrameric type II transmembrane endocytic vertebrate receptor that binds chitin, is found in human lung epithelium and modulates lung epithelial inflammatory responses to <jats:italic>A<\/jats:italic>. <jats:italic>fumigatus<\/jats:italic> cell wall polysaccharides. We previously reported the detrimental role of FIBCD1 in a murine model of pulmonary invasive aspergillosis. However, the effect that chitin and chitin-containing <jats:italic>A<\/jats:italic>. <jats:italic>fumigatus<\/jats:italic> conidia exerts on lung epithelium following exposure through FIBCD1 is not yet fully explored. Using both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> strategies, we examined how lung and lung epithelial gene expression are modified after exposure to fungal conidia or chitin fragments in the presence or absence of FIBCD1. FIBCD1 expression was associated with a decrease in inflammatory cytokines with increasing size of chitin (dimer-oligomer). Thus, our results demonstrate that FIBCD1 expression modulates cytokine and chemokine expression in response to <jats:italic>A<\/jats:italic>. <jats:italic>fumigatus<\/jats:italic> conidia that is modified by the presence of chitin particles.<\/jats:p>","DOI":"10.1371\/journal.pone.0282347","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T18:40:41Z","timestamp":1678300841000},"page":"e0282347","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["The role of FIBCD1 in response to Aspergillus fumigatus in lung epithelial cells"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6214-4235","authenticated-orcid":true,"given":"Shreya","family":"Bhattacharya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alec Jacob","family":"Maupin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders Gr\u00f8nnegaard","family":"Schlosser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernst-Martin","family":"F\u00fcchtbauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9118-8779","authenticated-orcid":true,"given":"Yamel Cardona","family":"Gloria","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-7056","authenticated-orcid":true,"given":"Alexander N. R.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uffe","family":"Holmskov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-8037","authenticated-orcid":true,"given":"Jesper Bonnet","family":"Moeller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven P.","family":"Templeton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"issue":"5258","key":"pone.0282347.ref001","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1126\/science.272.5258.50","article-title":"The instructive role of innate immunity in the acquired immune response","volume":"272","author":"DT Fearon","year":"1996","journal-title":"Science"},{"issue":"24","key":"pone.0282347.ref002","doi-asserted-by":"crossref","first-page":"13938","DOI":"10.1073\/pnas.96.24.13938","article-title":"Ligation of intestinal epithelial CD1d induces bioactive IL-10: critical role of the cytoplasmic tail in autocrine signaling","volume":"96","author":"SP Colgan","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0282347.ref003","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-micro-030117-020406","article-title":"The Cell Wall of the Human Fungal Pathogen Aspergillus fumigatus: Biosynthesis, Organization, Immune Response, and Virulence","volume":"71","author":"J-P Latg\u00e9","year":"2017","journal-title":"Annual Review of Microbiology"},{"issue":"2","key":"pone.0282347.ref004","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1365-2958.2007.05872.x","article-title":"The cell wall: a carbohydrate armour for the fungal cell","volume":"66","author":"JP Latg\u00e9","year":"2007","journal-title":"Mol Microbiol"},{"issue":"6","key":"pone.0282347.ref005","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.4049\/jimmunol.0802113","article-title":"Chitin is a size-dependent regulator of macrophage TNF and IL-10 production","volume":"182","author":"CA Da Silva","year":"2009","journal-title":"J Immunol"},{"issue":"4","key":"pone.0282347.ref006","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.mib.2010.05.002","article-title":"Chitin synthesis and fungal pathogenesis","volume":"13","author":"MD Lenardon","year":"2010","journal-title":"Current Opinion in Microbiology"},{"issue":"3","key":"pone.0282347.ref007","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.immuni.2014.02.003","article-title":"Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and \u03b3\u03b4 T cells","volume":"40","author":"SJ Van Dyken","year":"2014","journal-title":"Immunity"},{"issue":"7140","key":"pone.0282347.ref008","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature05746","article-title":"Chitin induces accumulation in tissue of innate immune cells associated with allergy","volume":"447","author":"TA Reese","year":"2007","journal-title":"Nature"},{"issue":"2","key":"pone.0282347.ref009","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12016-017-8600-0","article-title":"Chitin and Its Effects on Inflammatory and Immune Responses","volume":"54","author":"D Elieh Ali Komi","year":"2018","journal-title":"Clin Rev Allergy Immunol"},{"issue":"6","key":"pone.0282347.ref010","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.coi.2008.10.002","article-title":"Chitin regulation of immune responses: an old molecule with new roles","volume":"20","author":"CG Lee","year":"2008","journal-title":"Curr Opin Immunol"},{"issue":"6","key":"pone.0282347.ref011","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1128\/IAI.70.6.3156-3163.2002","article-title":"Uptake of Aspergillus fumigatus Conidia by phagocytic and nonphagocytic cells in vitro: quantitation using strains expressing green fluorescent protein","volume":"70","author":"JA Wasylnka","year":"2002","journal-title":"Infect Immun"},{"key":"pone.0282347.ref012","first-page":"19","article-title":"The fungal ligand chitin directly binds TLR2 and triggers inflammation dependent on oligomer size","author":"K Fuchs","year":"2018","journal-title":"EMBO Rep"},{"issue":"1","key":"pone.0282347.ref013","doi-asserted-by":"crossref","first-page":"C62","DOI":"10.1152\/ajpcell.00268.2017","article-title":"Phagocytosis-mediated M1 activation by chitin but not by chitosan","volume":"315","author":"S Davis","year":"2018","journal-title":"American journal of physiology Cell physiology"},{"issue":"8","key":"pone.0282347.ref014","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1128\/IAI.01990-14","article-title":"Eosinophils are recruited in response to chitin exposure and enhance Th2-mediated immune pathology in Aspergillus fumigatus infection","volume":"82","author":"EM O\u2019Dea","year":"2014","journal-title":"Infect Immun"},{"issue":"12","key":"pone.0282347.ref015","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1164\/rccm.200912-1877OC","article-title":"Chitin particles are multifaceted immune adjuvants","volume":"182","author":"CA Da Silva","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"pone.0282347.ref016","doi-asserted-by":"crossref","first-page":"956","DOI":"10.4049\/jimmunol.1900174","article-title":"The Metabolic Cytokine Adiponectin Inhibits Inflammatory Lung Pathology in Invasive Aspergillosis","volume":"203","author":"N Amarsaikhan","year":"2019","journal-title":"The Journal of Immunology"},{"issue":"3","key":"pone.0282347.ref017","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.4049\/jimmunol.164.3.1314","article-title":"Oral administration of chitin down-regulates serum IgE levels and lung eosinophilia in the allergic mouse","volume":"164","author":"Y Shibata","year":"2000","journal-title":"J Immunol"},{"issue":"1967","key":"pone.0282347.ref018","article-title":"FIBCD1 Binds Aspergillus fumigatus and Regulates Lung Epithelial Response to Cell Wall Components","volume":"9","author":"CS Jepsen","year":"2018","journal-title":"Frontiers in Immunology"},{"issue":"12","key":"pone.0282347.ref019","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1084\/jem.20182244","article-title":"Modulation of the fungal mycobiome is regulated by the chitin-binding receptor FIBCD1","volume":"216","author":"JB Moeller","year":"2019","journal-title":"J Exp Med"},{"issue":"6","key":"pone.0282347.ref020","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.4049\/jimmunol.0901526","article-title":"Characterization of FIBCD1 as an acetyl group-binding receptor that binds chitin","volume":"183","author":"A Schlosser","year":"2009","journal-title":"J Immunol"},{"issue":"8","key":"pone.0282347.ref021","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1080\/21505594.2016.1278337","article-title":"M-ficolin is present in Aspergillus fumigatus infected lung and modulates epithelial cell immune responses elicited by fungal cell wall polysaccharides","volume":"8","author":"K Jensen","year":"2017","journal-title":"Virulence"},{"issue":"12","key":"pone.0282347.ref022","doi-asserted-by":"crossref","first-page":"983","DOI":"10.4049\/immunohorizons.2100092","article-title":"FIBCD1 Deficiency Decreases Disease Severity in a Murine Model of Invasive Pulmonary Aspergillosis","volume":"5","author":"S Bhattacharya","year":"2021","journal-title":"ImmunoHorizons"},{"issue":"9","key":"pone.0282347.ref023","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1093\/nar\/gkt178","article-title":"Translating mRNAs strongly correlate to proteins in a multivariate manner and their translation ratios are phenotype specific","volume":"41","author":"T Wang","year":"2013","journal-title":"Nucleic Acids Research"},{"issue":"1","key":"pone.0282347.ref024","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1038\/s41598-017-03057-5","article-title":"Single-cell protein-mRNA correlation analysis enabled by multiplexed dual-analyte co-detection","volume":"7","author":"H Gong","year":"2017","journal-title":"Scientific Reports"},{"issue":"6","key":"pone.0282347.ref025","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.4049\/jimmunol.181.6.4279","article-title":"TLR-2 and IL-17A in Chitin-Induced Macrophage Activation and Acute Inflammation","volume":"181","author":"CA Da Silva","year":"2008","journal-title":"The Journal of Immunology"},{"key":"pone.0282347.ref026","first-page":"6","article-title":"Anti-Immune Strategies of Pathogenic Fungi","author":"CM Marcos","year":"2016","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"issue":"3","key":"pone.0282347.ref027","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1080\/13693780802209082","article-title":"Fungal strategies for overcoming host innate immune response","volume":"47","author":"LYA Chai","year":"2009","journal-title":"Medical Mycology"},{"issue":"1","key":"pone.0282347.ref028","doi-asserted-by":"crossref","first-page":"e13272","DOI":"10.1111\/cmi.13272","article-title":"Fungal factors involved in host immune evasion, modulation and exploitation during infection","volume":"23","author":"A K\u00f6nig","year":"2021","journal-title":"Cellular Microbiology"},{"key":"pone.0282347.ref029","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1146\/annurev-physiol-012110-142250","article-title":"Role of chitin and chitinase\/chitinase-like proteins in inflammation, tissue remodeling, and injury","volume":"73","author":"CG Lee","year":"2011","journal-title":"Annual review of physiology"},{"issue":"21","key":"pone.0282347.ref030","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1016\/j.jmb.2019.03.027","article-title":"Menacing Mold: Recent Advances in Aspergillus Pathogenesis and Host Defense","volume":"431","author":"BY Tischler","year":"2019","journal-title":"J Mol Biol"},{"issue":"4","key":"pone.0282347.ref031","doi-asserted-by":"crossref","first-page":"e12925","DOI":"10.1111\/sji.12925","article-title":"Fungal recognition by mammalian fibrinogen-related proteins","volume":"92","author":"B Pilecki","year":"2020","journal-title":"Scandinavian Journal of Immunology"},{"issue":"6","key":"pone.0282347.ref032","doi-asserted-by":"crossref","first-page":"548","DOI":"10.3390\/jof8060548","article-title":"Respiratory Epithelial Cells: More Than Just a Physical Barrier to Fungal Infections","volume":"8","author":"BCSC Barros","year":"2022","journal-title":"Journal of Fungi"},{"issue":"4","key":"pone.0282347.ref033","doi-asserted-by":"crossref","DOI":"10.3390\/molecules19044433","article-title":"The Effect of Chitin Size, Shape, Source and Purification Method on Immune Recognition","volume":"19","author":"FJ Alvarez","year":"2014","journal-title":"Molecules"},{"issue":"1","key":"pone.0282347.ref034","doi-asserted-by":"crossref","first-page":"e1003080","DOI":"10.1371\/journal.ppat.1003080","article-title":"Innate sensing of chitin and chitosan","volume":"9","author":"CL Bueter","year":"2013","journal-title":"PLoS Pathog"},{"key":"pone.0282347.ref035","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s12281-009-0023-9","article-title":"Recognition of the fungal cell wall by innate immune receptors","volume":"3","author":"S Levitz","year":"2009","journal-title":"Current Fungal Infection Reports"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T18:41:09Z","timestamp":1678300869000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282347"}},"subtitle":[],"editor":[{"given":"Olaf","family":"Kniemeyer","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0282347","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]}}}