Publicação
Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus
| Resumo: | Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans. |
|---|---|
| Autores principais: | Stappers, Mark H.T. |
| Outros Autores: | Clark, Alexandra E.; Aimanianda, Vishukumar; Bidula, Stefan; Reid, Delyth M.; Asamaphan, Patawee; Hardison, Sarah E.; Dambuza, Ivy M.; Valsecchi, Isabel; Kerscher, Bernhard; Plato, Anthony; Wallace, Carol A.; Yuecel, Raif; Hebecker, Betty; Sousa, Maria da Glória Teixeira; Cunha, Cristina; Liu, Yan; Feizi, Ten; Brakhage, Axel A.; Kwon-Chung, Kyung J.; Gow, Neil A.R.; Zanda, Matteo; Piras, Monica; Zanato, Chiara; Jaeger, Martin; Netea, Mihai G.; Van De Veerdonk, Frank L.; Lacerda, João F.; Campos, António; Carvalho, Agostinho; Willment, Janet A.; Latgé, Jean Paul; Brown, Gordon D. |
| Assunto: | Animals Aspergillosis Aspergillus fumigatus Cell Wall Female Humans Lectins, C-Type Macrophages Melanins Mice Mice, Inbred C57BL Naphthols Rats Rats, Sprague-Dawley Spores, Fungal Substrate Specificity |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867439790007255040 |
|---|---|
| author | Stappers, Mark H.T. |
| author2 | Clark, Alexandra E. Aimanianda, Vishukumar Bidula, Stefan Reid, Delyth M. Asamaphan, Patawee Hardison, Sarah E. Dambuza, Ivy M. Valsecchi, Isabel Kerscher, Bernhard Plato, Anthony Wallace, Carol A. Yuecel, Raif Hebecker, Betty Sousa, Maria da Glória Teixeira Cunha, Cristina Liu, Yan Feizi, Ten Brakhage, Axel A. Kwon-Chung, Kyung J. Gow, Neil A.R. Zanda, Matteo Piras, Monica Zanato, Chiara Jaeger, Martin Netea, Mihai G. Van De Veerdonk, Frank L. Lacerda, João F. Campos, António Carvalho, Agostinho Willment, Janet A. Latgé, Jean Paul Brown, Gordon D. |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Stappers, Mark H.T. Clark, Alexandra E. Aimanianda, Vishukumar Bidula, Stefan Reid, Delyth M. Asamaphan, Patawee Hardison, Sarah E. Dambuza, Ivy M. Valsecchi, Isabel Kerscher, Bernhard Plato, Anthony Wallace, Carol A. Yuecel, Raif Hebecker, Betty Sousa, Maria da Glória Teixeira Cunha, Cristina Liu, Yan Feizi, Ten Brakhage, Axel A. Kwon-Chung, Kyung J. Gow, Neil A.R. Zanda, Matteo Piras, Monica Zanato, Chiara Jaeger, Martin Netea, Mihai G. Van De Veerdonk, Frank L. Lacerda, João F. Campos, António Carvalho, Agostinho Willment, Janet A. Latgé, Jean Paul Brown, Gordon D. |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Stappers, Mark H.T.\"},{\"Person.name\":\"Clark, Alexandra E.\"},{\"Person.name\":\"Aimanianda, Vishukumar\"},{\"Person.name\":\"Bidula, Stefan\"},{\"Person.name\":\"Reid, Delyth M.\"},{\"Person.name\":\"Asamaphan, Patawee\"},{\"Person.name\":\"Hardison, Sarah E.\"},{\"Person.name\":\"Dambuza, Ivy M.\"},{\"Person.name\":\"Valsecchi, Isabel\"},{\"Person.name\":\"Kerscher, Bernhard\"},{\"Person.name\":\"Plato, Anthony\"},{\"Person.name\":\"Wallace, Carol A.\"},{\"Person.name\":\"Yuecel, Raif\"},{\"Person.name\":\"Hebecker, Betty\"},{\"Person.name\":\"Sousa, Maria da Glória Teixeira\"},{\"Person.name\":\"Cunha, Cristina\"},{\"Person.name\":\"Liu, Yan\"},{\"Person.name\":\"Feizi, Ten\"},{\"Person.name\":\"Brakhage, Axel A.\"},{\"Person.name\":\"Kwon-Chung, Kyung J.\"},{\"Person.name\":\"Gow, Neil A.R.\"},{\"Person.name\":\"Zanda, Matteo\"},{\"Person.name\":\"Piras, Monica\"},{\"Person.name\":\"Zanato, Chiara\"},{\"Person.name\":\"Jaeger, Martin\"},{\"Person.name\":\"Netea, Mihai G.\"},{\"Person.name\":\"Van De Veerdonk, Frank L.\"},{\"Person.name\":\"Lacerda, João F.\"},{\"Person.name\":\"Campos, António\"},{\"Person.name\":\"Carvalho, Agostinho\"},{\"Person.name\":\"Willment, Janet A.\"},{\"Person.name\":\"Latgé, Jean Paul\"},{\"Person.name\":\"Brown, Gordon D.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Stappers, Mark H.T. Clark, Alexandra E. Aimanianda, Vishukumar Bidula, Stefan Reid, Delyth M. Asamaphan, Patawee Hardison, Sarah E. Dambuza, Ivy M. Valsecchi, Isabel Kerscher, Bernhard Plato, Anthony Wallace, Carol A. Yuecel, Raif Hebecker, Betty Sousa, Maria da Glória Teixeira Cunha, Cristina Liu, Yan Feizi, Ten Brakhage, Axel A. Kwon-Chung, Kyung J. Gow, Neil A.R. Zanda, Matteo Piras, Monica Zanato, Chiara Jaeger, Martin Netea, Mihai G. Van De Veerdonk, Frank L. Lacerda, João F. Campos, António Carvalho, Agostinho Willment, Janet A. Latgé, Jean Paul Brown, Gordon D. |
| datacite.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2019-07-01T06:02:43Z |
| datacite.date.embargoed.fl_str_mv | 2019-07-01T06:02:43Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Animals Aspergillosis Aspergillus fumigatus Cell Wall Female Humans Lectins, C-Type Macrophages Melanins Mice Mice, Inbred C57BL Naphthols Rats Rats, Sprague-Dawley Spores, Fungal Substrate Specificity |
| datacite.titles.title.fl_str_mv | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Stappers, Mark H.T. Clark, Alexandra E. Aimanianda, Vishukumar Bidula, Stefan Reid, Delyth M. Asamaphan, Patawee Hardison, Sarah E. Dambuza, Ivy M. Valsecchi, Isabel Kerscher, Bernhard Plato, Anthony Wallace, Carol A. Yuecel, Raif Hebecker, Betty Sousa, Maria da Glória Teixeira Cunha, Cristina Liu, Yan Feizi, Ten Brakhage, Axel A. Kwon-Chung, Kyung J. Gow, Neil A.R. Zanda, Matteo Piras, Monica Zanato, Chiara Jaeger, Martin Netea, Mihai G. Van De Veerdonk, Frank L. Lacerda, João F. Campos, António Carvalho, Agostinho Willment, Janet A. Latgé, Jean Paul Brown, Gordon D. |
| dc.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2019-07-01T06:02:43Z |
| dc.date.embargoed.fl_str_mv | 2019-07-01T06:02:43Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/58070 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Macmillan Publishers |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Animals Aspergillosis Aspergillus fumigatus Cell Wall Female Humans Lectins, C-Type Macrophages Melanins Mice Mice, Inbred C57BL Naphthols Rats Rats, Sprague-Dawley Spores, Fungal Substrate Specificity |
| dc.title.fl_str_mv | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/cc6ed110-8465-4a90-abfe-4e9e52b105bf/download |
| id | rum_5236afa78a4bb7059c4e7e4e6ac8165b |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/58070 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/58070 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Stappers, Mark H.T. Clark, Alexandra E. Aimanianda, Vishukumar Bidula, Stefan Reid, Delyth M. Asamaphan, Patawee Hardison, Sarah E. Dambuza, Ivy M. Valsecchi, Isabel Kerscher, Bernhard Plato, Anthony Wallace, Carol A. Yuecel, Raif Hebecker, Betty Sousa, Maria da Glória Teixeira Cunha, Cristina Liu, Yan Feizi, Ten Brakhage, Axel A. Kwon-Chung, Kyung J. Gow, Neil A.R. Zanda, Matteo Piras, Monica Zanato, Chiara Jaeger, Martin Netea, Mihai G. Van De Veerdonk, Frank L. Lacerda, João F. Campos, António Carvalho, Agostinho Willment, Janet A. Latgé, Jean Paul Brown, Gordon D. |
| publishDate | 2018 |
| publisher.none.fl_str_mv | Macmillan Publishers |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engMacmillan PublishersporResistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.application/pdfporRecognition of DHN-melanin by a C-type lectin receptor is required for immunity to AspergillusStappers, Mark H.T.Clark, Alexandra E.Aimanianda, VishukumarBidula, StefanReid, Delyth M.Asamaphan, PataweeHardison, Sarah E.Dambuza, Ivy M.Valsecchi, IsabelKerscher, BernhardPlato, AnthonyWallace, Carol A.Yuecel, RaifHebecker, BettySousa, Maria da Glória TeixeiraCunha, CristinaLiu, YanFeizi, TenBrakhage, Axel A.Kwon-Chung, Kyung J.Gow, Neil A.R.Zanda, MatteoPiras, MonicaZanato, ChiaraJaeger, MartinNetea, Mihai G.Van De Veerdonk, Frank L.Lacerda, João F.Campos, AntónioCarvalho, AgostinhoWillment, Janet A.Latgé, Jean PaulBrown, Gordon D.HostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptPMID29489751ISSNIsPartOf0028-0836EISSNIsPartOf1476-4687DOIIsPartOf10.1038/nature259742019-07-01T06:02:43Z20182018-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/58070http://purl.org/coar/access_right/c_abf2open accessAnimalsAspergillosisAspergillus fumigatusCell WallFemaleHumansLectins, C-TypeMacrophagesMelaninsMiceMice, Inbred C57BLNaphtholsRatsRats, Sprague-DawleySpores, FungalSubstrate Specificity6036518 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/cc6ed110-8465-4a90-abfe-4e9e52b105bf/download |
| spellingShingle | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus Stappers, Mark H.T. Animals Aspergillosis Aspergillus fumigatus Cell Wall Female Humans Lectins, C-Type Macrophages Melanins Mice Mice, Inbred C57BL Naphthols Rats Rats, Sprague-Dawley Spores, Fungal Substrate Specificity |
| status | SINGLETON |
| subject.fl_str_mv | Animals Aspergillosis Aspergillus fumigatus Cell Wall Female Humans Lectins, C-Type Macrophages Melanins Mice Mice, Inbred C57BL Naphthols Rats Rats, Sprague-Dawley Spores, Fungal Substrate Specificity |
| title | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus |
| title_full | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus |
| title_fullStr | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus |
| title_full_unstemmed | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus |
| title_short | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus |
| title_sort | Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus |
| topic | Animals Aspergillosis Aspergillus fumigatus Cell Wall Female Humans Lectins, C-Type Macrophages Melanins Mice Mice, Inbred C57BL Naphthols Rats Rats, Sprague-Dawley Spores, Fungal Substrate Specificity |
| topic_facet | Animals Aspergillosis Aspergillus fumigatus Cell Wall Female Humans Lectins, C-Type Macrophages Melanins Mice Mice, Inbred C57BL Naphthols Rats Rats, Sprague-Dawley Spores, Fungal Substrate Specificity |
| url | https://hdl.handle.net/1822/58070 |
| visible | 1 |