Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing
IntroductionChitin is a highly abundant polysaccharide in nature and is linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent inmammals and plants and, thus, represents a microbeassociatedmolecular pattern (MAMP). However, highly po...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-03-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497174/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850042377552527360 |
|---|---|
| author | Tzu-Hsuan Chang Yamel Cardona Gloria Margareta J. Hellmann Timmy Richardo Carsten Leo Greve Didier Le Roy Thierry Roger Francesca Bork Stefanie Bugl Johanna Jakob Johannes Sonnberger Lydia Kasper Bernhard Hube Bernhard Hube Stefan Pusch Neil A. R. Gow Morten Sørlie Anne Tøndervik Bruno M. Moerschbacher Alexander N. R. Weber Alexander N. R. Weber Alexander N. R. Weber Alexander N. R. Weber |
| author_facet | Tzu-Hsuan Chang Yamel Cardona Gloria Margareta J. Hellmann Timmy Richardo Carsten Leo Greve Didier Le Roy Thierry Roger Francesca Bork Stefanie Bugl Johanna Jakob Johannes Sonnberger Lydia Kasper Bernhard Hube Bernhard Hube Stefan Pusch Neil A. R. Gow Morten Sørlie Anne Tøndervik Bruno M. Moerschbacher Alexander N. R. Weber Alexander N. R. Weber Alexander N. R. Weber Alexander N. R. Weber |
| author_sort | Tzu-Hsuan Chang |
| collection | DOAJ |
| description | IntroductionChitin is a highly abundant polysaccharide in nature and is linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent inmammals and plants and, thus, represents a microbeassociatedmolecular pattern (MAMP). However, highly polymeric chitin is insoluble, which potentially hampers recognition by host immune sensors. In plants, secreted chitinases degrade polymeric chitin into diffusible oligomers, which are “fed to” innate immune receptors and co-receptors. In human and murine immune cells, a similar enzymatic activity was shown for human chitotriosidase (CHIT1), and oligomeric chitin is sensed via an innate immune receptor, Toll-like receptor (TLR) 2. However, a complete system of generating MAMPs from chitin and feeding them into a specific receptor/co-receptor-aided sensing mechanism has remained unknown in mammals.MethodsThe effect of the secreted chitinolytic host enzyme, CHIT1, on the TLR2 activity of polymeric chitin preparations from shrimps, house dust mites and the fungal pathogen Candida albicans was assessed in vitro using cell lines and primary immune cells. Moreover, the regulation of CHIT1 was analyzed.ResultsHere, we show that CHIT1 converts inert polymeric chitin into diffusible oligomers that can be sensed by TLR1/TLR2 co-receptor/receptor heterodimers, a process promoted by the lipopolysaccharide binding protein (LBP) and CD14. Furthermore, we observed that Chit1 is induced via the b-glucan receptor Dectin-1 upon direct contact of immortalized human macrophages to the fungal pathogen Candida albicans, whereas the defined fungal secreted aspartyl proteases, Sap2 and Sap6, from C. albicans were able to degrade CHIT1 in vitro.DiscussionOur study shows the existence of an inducible system of MAMP generation in the human host that enables contact-independent immune activation by diffusible MAMP ligands with a striking similarity to the plant kingdom. Moreover, this study highlights CHIT1 as a potential therapeutic target for TLR2-mediated inflammatory processes that are fueled by oligomeric chitin. |
| format | Article |
| id | doaj-art-776f6d1d58574e4f8bf9e1a087da75dc |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-776f6d1d58574e4f8bf9e1a087da75dc2025-08-20T02:55:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.14971741497174Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensingTzu-Hsuan Chang0Yamel Cardona Gloria1Margareta J. Hellmann2Timmy Richardo3Carsten Leo Greve4Didier Le Roy5Thierry Roger6Francesca Bork7Stefanie Bugl8Johanna Jakob9Johannes Sonnberger10Lydia Kasper11Bernhard Hube12Bernhard Hube13Stefan Pusch14Neil A. R. Gow15Morten Sørlie16Anne Tøndervik17Bruno M. Moerschbacher18Alexander N. R. Weber19Alexander N. R. Weber20Alexander N. R. Weber21Alexander N. R. Weber22Department of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, GermanyDepartment of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, GermanyInstitute for Biology and Biotechnology of Plants, University of Münster, Münster, GermanyDepartment of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, GermanyDepartment of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, GermanyInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandDepartment of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, GermanyDepartment of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, GermanyDepartment of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, GermanyDepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, GermanyDepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, GermanyDepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, GermanyInstitute of Microbiology, Friedrich Schiller University, Jena, GermanyDepartment of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg and German Cancer Consortium (DKTK), Clinical Cooperation Unit (CCU) Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Biosciences, Medical Research Council Centre for Medical Mycology at The University of Exeter, University of Exeter, Exeter, United KingdomDepartment of Chemistry, Biotechnology, and Food Science, Norwegian University of Life Sciences, Ås, NorwayDepartment of Biotechnology and Nanomedicine, Stiftelsen for Industriell og Teknisk Forskning (SINTEF) Industry, Trondheim, NorwayInstitute for Biology and Biotechnology of Plants, University of Münster, Münster, GermanyDepartment of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, Germany0iFIT – Cluster of Excellence (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany1CMFI – Cluster of Excellence (EXC 2124) “Controlling Microbes to Fight Infection”, University of Tübingen, Tübingen, Germany2Deutsches Konsortium für Translationale Krebsforschung (DKTK; German Cancer Consortium), Partner Site Tübingen, Department of Immunology, University of Tübingen, Tübingen, GermanyIntroductionChitin is a highly abundant polysaccharide in nature and is linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent inmammals and plants and, thus, represents a microbeassociatedmolecular pattern (MAMP). However, highly polymeric chitin is insoluble, which potentially hampers recognition by host immune sensors. In plants, secreted chitinases degrade polymeric chitin into diffusible oligomers, which are “fed to” innate immune receptors and co-receptors. In human and murine immune cells, a similar enzymatic activity was shown for human chitotriosidase (CHIT1), and oligomeric chitin is sensed via an innate immune receptor, Toll-like receptor (TLR) 2. However, a complete system of generating MAMPs from chitin and feeding them into a specific receptor/co-receptor-aided sensing mechanism has remained unknown in mammals.MethodsThe effect of the secreted chitinolytic host enzyme, CHIT1, on the TLR2 activity of polymeric chitin preparations from shrimps, house dust mites and the fungal pathogen Candida albicans was assessed in vitro using cell lines and primary immune cells. Moreover, the regulation of CHIT1 was analyzed.ResultsHere, we show that CHIT1 converts inert polymeric chitin into diffusible oligomers that can be sensed by TLR1/TLR2 co-receptor/receptor heterodimers, a process promoted by the lipopolysaccharide binding protein (LBP) and CD14. Furthermore, we observed that Chit1 is induced via the b-glucan receptor Dectin-1 upon direct contact of immortalized human macrophages to the fungal pathogen Candida albicans, whereas the defined fungal secreted aspartyl proteases, Sap2 and Sap6, from C. albicans were able to degrade CHIT1 in vitro.DiscussionOur study shows the existence of an inducible system of MAMP generation in the human host that enables contact-independent immune activation by diffusible MAMP ligands with a striking similarity to the plant kingdom. Moreover, this study highlights CHIT1 as a potential therapeutic target for TLR2-mediated inflammatory processes that are fueled by oligomeric chitin.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497174/fullchitinchitotriosidaseN-acetyl-glucosamineToll-like receptor (TLR)inflammationmyeloid cell |
| spellingShingle | Tzu-Hsuan Chang Yamel Cardona Gloria Margareta J. Hellmann Timmy Richardo Carsten Leo Greve Didier Le Roy Thierry Roger Francesca Bork Stefanie Bugl Johanna Jakob Johannes Sonnberger Lydia Kasper Bernhard Hube Bernhard Hube Stefan Pusch Neil A. R. Gow Morten Sørlie Anne Tøndervik Bruno M. Moerschbacher Alexander N. R. Weber Alexander N. R. Weber Alexander N. R. Weber Alexander N. R. Weber Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing Frontiers in Immunology chitin chitotriosidase N-acetyl-glucosamine Toll-like receptor (TLR) inflammation myeloid cell |
| title | Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing |
| title_full | Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing |
| title_fullStr | Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing |
| title_full_unstemmed | Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing |
| title_short | Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing |
| title_sort | transkingdom mechanism of mamp generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into tlr2 mediated innate immune sensing |
| topic | chitin chitotriosidase N-acetyl-glucosamine Toll-like receptor (TLR) inflammation myeloid cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497174/full |
| work_keys_str_mv | AT tzuhsuanchang transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT yamelcardonagloria transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT margaretajhellmann transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT timmyrichardo transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT carstenleogreve transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT didierleroy transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT thierryroger transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT francescabork transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT stefaniebugl transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT johannajakob transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT johannessonnberger transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT lydiakasper transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT bernhardhube transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT bernhardhube transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT stefanpusch transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT neilargow transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT mortensørlie transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT annetøndervik transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT brunommoerschbacher transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT alexandernrweber transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT alexandernrweber transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT alexandernrweber transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing AT alexandernrweber transkingdommechanismofmampgenerationbychitotriosidasefeedsoligomericchitinfromfungalpathogensandallergensintotlr2mediatedinnateimmunesensing |