{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:52:43Z","timestamp":1782456763599,"version":"3.54.5"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Mammalian cells do not produce chitin, an insoluble polymer of N-acetyl-D-glucosamine (GlcNAc), although chitin is a structural component of the cell wall of pathogenic microorganisms such as Candida albicans. Mammalian cells, including cells of the innate immune system elaborate chitinases, including chitotriosidase (Chit1), which may play a role in the anti-fungal immune response. In the current study, using knockout mice, we determined the role of Chit1 against systemic candidiasis. Chit1-deficient mice showed significant decrease in kidney fungal burden compared to mice expressing the functional enzyme. Using<jats:italic>in vitro<\/jats:italic>anti-candidal neutrophil functional assays, the introduction of the Chit1:chitin digestion end-product, chitobiose (N-acetyl-D-glucosamine dimer, GlcNAc2), decreased fungal-induced neutrophil swarming and Candida killing<jats:italic>in vitro<\/jats:italic>. Also, a role for the lectin-like binding site on the neutrophil integrin CR3 (Mac-1, CD11b\/CD18) was found through physiological competitive interference by chitobiose. Furthermore, chitobiose treatment of wild type mice during systemic candidiasis resulted in the significant increase in fungal burden in the kidney. These data suggest a counterproductive role of Chit1 in mounting an efficient anti-fungal defense against systemic candidiasis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.626798","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T04:50:50Z","timestamp":1615870250000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic Candidiasis"],"prefix":"10.3389","volume":"12","author":[{"given":"Nicholas A.","family":"Schmitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritesh P.","family":"Thakare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Shiang","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Min","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack A.","family":"Elias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Geun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"LeBlanc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1086\/321811","article-title":"Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey","volume":"33","author":"Blumberg","year":"2001","journal-title":"Clin Infect Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"359","DOI":"10.4161\/viru.1.5.12795","article-title":"Candida infection and colonization among non-trauma emergency surgery patients","volume":"1","author":"Kourkoumpetis","year":"2010","journal-title":"Virulence."},{"key":"B3","doi-asserted-by":"publisher","first-page":"367","DOI":"10.4161\/viru.1.5.12796","article-title":"Candida infection and colonization among trauma patients","volume":"1","author":"Manolakaki","year":"2010","journal-title":"Virulence"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.semcdb.2018.06.004","article-title":"Mammalian innate immunity to fungal infection","volume":"89","author":"Brown","year":"2019","journal-title":"Semin Cell Dev Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.mib.2016.08.006","article-title":"Cell biology of Candida albicans-host interactions","volume":"34","author":"da Silva","year":"2016","journal-title":"Curr Opin Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1111\/imr.12454","article-title":"How neutrophils kill fungi","volume":"273","author":"Gazendam","year":"2016","journal-title":"Immunol Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.semcdb.2018.02.026","article-title":"Candida innate immunity at the mucosa","volume":"89","author":"Richardson","year":"2019","journal-title":"Semin Cell Dev Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.molimm.2009.09.018","article-title":"Complement receptor 3, not Dectin-1, is the major receptor on human neutrophils for beta-glucan-bearing particles","volume":"47","author":"van Bruggen","year":"2009","journal-title":"Mol Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1083\/jcb.120.4.1031","article-title":"The I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b\/CD18) for four distinct adhesion ligands","volume":"120","author":"Diamond","year":"1993","journal-title":"J Cell Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3337","DOI":"10.1074\/jbc.M111.298307","article-title":"Lectin site ligation of CR3 induces conformational changes and signaling","volume":"287","author":"O'Brien","year":"2012","journal-title":"J Biol Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"6417","DOI":"10.4049\/jimmunol.169.11.6417","article-title":"Function of the lectin domain of Mac-1\/complement receptor type 3 (CD11b\/CD18) in regulating neutrophil adhesion","volume":"169","author":"Xia","year":"2002","journal-title":"J Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"4136","DOI":"10.4049\/jimmunol.1202671","article-title":"An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to Candida albicans","volume":"190","author":"Byrd","year":"2013","journal-title":"J Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.mib.2010.05.002","article-title":"Chitin synthesis and fungal pathogenesis","volume":"13","author":"Lenardon","year":"2010","journal-title":"Curr Opin Microbiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1093\/intimm\/dxh328","article-title":"Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity","volume":"17","author":"M. van Eijk","year":"2005","journal-title":"Int Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s11010-012-1506-5","article-title":"Evaluation of AMCase and CHIT-1 expression in monocyte macrophages lineage","volume":"374","author":"Di Rosa","year":"2013","journal-title":"Mol Cell Biochem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/j.1365-2230.2008.03092.x","article-title":"Expression. Purification and in vitro antifungal activity of acidic mammalian chitinase against Candida albicans, Aspergillus fumigatus and Trichophyton rubrum strains","volume":"34","author":"Chen","year":"2009","journal-title":"Clin Exp Dermatol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"14","DOI":"10.4168\/aair.2015.7.1.14","article-title":"Chitotriosidase in the Pathogenesis of Inflammation, Interstitial Lung Diseases and COPD","volume":"7","author":"Cho","year":"2015","journal-title":"Allergy Asthma Immunol Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2682680","DOI":"10.1155\/2016\/2682680","article-title":"Immunomodulatory effects of chitotriosidase enzyme","volume":"2016","author":"Elmonem","year":"2016","journal-title":"Enzyme Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1007\/s00018-009-8765-7","article-title":"Chitotriosidase and gene therapy for fungal infections","volume":"66","author":"Gordon-Thomson","year":"2009","journal-title":"Cell Mol Life Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1111\/j.1651-2227.1998.tb01515.x","article-title":"Serial chitotriosidase activity estimations in neonatal systemic candidiasis","volume":"87","author":"Labadaridis","year":"1998","journal-title":"Acta Paediatr."},{"key":"B21","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.4049\/jimmunol.156.3.1235","article-title":"Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b\/CD18)","volume":"156","author":"Thornton","year":"1996","journal-title":"J Immunol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.4049\/jimmunol.134.5.3307","article-title":"Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b","volume":"134","author":"Ross","year":"1985","journal-title":"J Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.4049\/jimmunol.1201115","article-title":"Chitinase 1 is a biomarker for and therapeutic target in scleroderma-associated interstitial lung disease that augments TGF-beta1 signaling","volume":"189","author":"Lee","year":"2012","journal-title":"J Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"318","DOI":"10.4049\/jimmunol.1502381","article-title":"Integrin cross-talk regulates the human neutrophil response to fungal beta-glucan in the context of the extracellular matrix: a prominent role for VLA3 in the antifungal response","volume":"198","author":"Johnson","year":"2017","journal-title":"J Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"920459","DOI":"10.1155\/2012\/920459","article-title":"Chitin, chitinase responses, and invasive fungal infections","volume":"2012","author":"Vega","year":"2012","journal-title":"Int J Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1074\/mcp.M500143-MCP200","article-title":"Proteomic analysis of human neutrophil granules","volume":"4","author":"Lominadze","year":"2005","journal-title":"Mol Cell Proteomics."},{"key":"B27","doi-asserted-by":"publisher","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":"B28","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S0009-8981(01)00398-9","article-title":"Plasma chitotriosidase activity in beta-thalassemia major: a comparative study between Sicilian and Sardinian patients","volume":"306","author":"Barone","year":"2001","journal-title":"Clin Chim Acta."},{"key":"B29","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1161\/01.ATV.19.3.687","article-title":"Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages","volume":"19","author":"Boot","year":"1999","journal-title":"Arterioscler Thromb Vasc Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1111\/j.1460-9568.2006.04780.x","article-title":"Chitotriosidase and inflammatory mediator levels in Alzheimer's disease and cerebrovascular dementia","volume":"23","author":"Di Rosa","year":"2006","journal-title":"Eur J Neurosci."},{"key":"B31","first-page":"977","article-title":"Chitotriosidase genotype and plasma activity in patients type 1 Gaucher's disease and their relatives (carriers and non carriers)","volume":"86","author":"Giraldo","year":"2001","journal-title":"Haematologica."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1038\/sj.leu.2403922","article-title":"Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia","volume":"19","author":"Lehrnbecher","year":"2005","journal-title":"Leukemia."},{"key":"B33","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/j.1567-1364.2005.00017.x","article-title":"Molecular organization of the cell wall of Candida albicans and its relation to pathogenicity","volume":"6","author":"Ruiz-Herrera","year":"2006","journal-title":"FEMS Yeast Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1111\/j.1462-5822.2005.00616.x","article-title":"Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence","volume":"7","author":"Kumamoto","year":"2005","journal-title":"Cell Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.micinf.2017.11.010","article-title":"Size matters - how the immune system deals with fungal hyphae","volume":"20","author":"Loffler","year":"2018","journal-title":"Microbes Infect."},{"key":"B36","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1021\/ml200008b","article-title":"Bisdionin C-a rationally designed, submicromolar inhibitor of family 18 chitinases","volume":"2","author":"Schuttelkopf","year":"2011","journal-title":"ACS Med Chem Lett."},{"key":"B37","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1248\/bpb.28.545","article-title":"Pharmacokinetics of chitobiose and chitotriose administered intravenously or orally to rats","volume":"28","author":"Chen","year":"2005","journal-title":"Biol Pharm Bull."},{"key":"B38","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1128\/9781555819583.ch12","article-title":"The fungal cell wall: structure, biosynthesis, and function","volume":"5","author":"Gow","year":"2017","journal-title":"Microbiol Spectr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1084\/jem.158.2.334","article-title":"Generation of three different fragments of bound C3 with purified factor I or serum. II. Location of binding sites in the C3 fragments for factors B and H. complement receptors, bovine conglutinin","volume":"158","author":"Ross","year":"1983","journal-title":"J Exp Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2478","DOI":"10.1182\/blood.V97.8.2478","article-title":"Mac-1 (CD11b\/CD18) is essential for Fc receptor-mediated neutrophil cytotoxicity and immunologic synapse formation","volume":"97","author":"van Spriel","year":"2001","journal-title":"Blood."},{"key":"B41","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1128\/IAI.70.2.517-527.2002","article-title":"Lymphocyte adhesion to Candida albicans","volume":"70","author":"Forsyth","year":"2002","journal-title":"Infect Immun."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.626798\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T06:10:28Z","timestamp":1698041428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.626798\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":41,"alternative-id":["10.3389\/fimmu.2021.626798"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.626798","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,16]]},"article-number":"626798"}}