Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections
| Autor(a) principal: | |
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| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/47593 |
Resumo: | © 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infectionsAspergillus fumigatusNADPH oxidaseCalcium signalingConidial melaninFlotillinFungal pathogenesisMacrophageMembrane microdomainsPhagolysosomevATPase© 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Lipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid-raft microdomains are essential components of phagolysosomal membranes of macrophages and depend on flotillins. Genetic deletion of flotillins demonstrates that the assembly of both major defense complexes vATPase and NADPH oxidase requires membrane microdomains. Furthermore, we describe a virulence mechanism leading to dysregulation of membrane microdomains by melanized wild-type conidia of the important human-pathogenic fungus Aspergillus fumigatus resulting in reduced phagolysosomal acidification. We show that phagolysosomes with ingested melanized conidia contain a reduced amount of free Ca2+ ions and that inhibition of Ca2+-dependent calmodulin activity led to reduced lipid-raft formation. We identify a single-nucleotide polymorphism in the human FLOT1 gene resulting in heightened susceptibility for invasive aspergillosis in hematopoietic stem cell transplant recipients. Collectively, flotillin-dependent microdomains on the phagolysosomal membrane play an essential role in protective antifungal immunity.This work was supported by the International Leibniz Research School ( ILRS ) as part of the excellence graduate school Jena School for Microbial Communication (JSMC) funded by the Deutsche Forschungsgemeinschaft ( DFG ), the Leibniz Science Campus “InfectoOptics,” and the DFG -funded CRC 127 8 “PolyTarget” (project B02 to A.A.B. and Z01 to M.T.F.). C.C. and A.C were supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund ( FEDER ) ( NORTE-01-0145-FEDER-000013 ), and by the Fundação para a Ciência e Tecnologia ( FCT ) ( SFRH/BPD/96176/2013 to C.C. and IF/00735/2014 to A.C.).ElsevierRepositório da Universidade de LisboaSchmidt, FranziskaThywißen, AndreasGoldmann, MarieCunha, CristinaCseresnyés, ZoltánSchmidt, HellaRafiq, MuhammadGaliani, SilviaGräler, Markus H.Chamilos, GeorgiosLacerda, JoãoCampos, AntónioEggeling, ChristianFigge, Marc ThiloHeinekamp, ThorstenFiller, Scott G.Carvalho, AgostinhoBrakhage, Axel A.2021-04-28T14:40:19Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47593engCell Rep. 2020 Aug 18;32(7):1080172211-124710.1016/j.celrep.2020.108017info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:50:36Zoai:repositorio.ul.pt:10451/47593Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:59:36.189047Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections |
| title |
Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections |
| spellingShingle |
Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections Schmidt, Franziska Aspergillus fumigatus NADPH oxidase Calcium signaling Conidial melanin Flotillin Fungal pathogenesis Macrophage Membrane microdomains Phagolysosome vATPase |
| title_short |
Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections |
| title_full |
Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections |
| title_fullStr |
Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections |
| title_full_unstemmed |
Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections |
| title_sort |
Flotillin-dependent membrane microdomains are required for functional phagolysosomes against fungal infections |
| author |
Schmidt, Franziska |
| author_facet |
Schmidt, Franziska Thywißen, Andreas Goldmann, Marie Cunha, Cristina Cseresnyés, Zoltán Schmidt, Hella Rafiq, Muhammad Galiani, Silvia Gräler, Markus H. Chamilos, Georgios Lacerda, João Campos, António Eggeling, Christian Figge, Marc Thilo Heinekamp, Thorsten Filler, Scott G. Carvalho, Agostinho Brakhage, Axel A. |
| author_role |
author |
| author2 |
Thywißen, Andreas Goldmann, Marie Cunha, Cristina Cseresnyés, Zoltán Schmidt, Hella Rafiq, Muhammad Galiani, Silvia Gräler, Markus H. Chamilos, Georgios Lacerda, João Campos, António Eggeling, Christian Figge, Marc Thilo Heinekamp, Thorsten Filler, Scott G. Carvalho, Agostinho Brakhage, Axel A. |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Schmidt, Franziska Thywißen, Andreas Goldmann, Marie Cunha, Cristina Cseresnyés, Zoltán Schmidt, Hella Rafiq, Muhammad Galiani, Silvia Gräler, Markus H. Chamilos, Georgios Lacerda, João Campos, António Eggeling, Christian Figge, Marc Thilo Heinekamp, Thorsten Filler, Scott G. Carvalho, Agostinho Brakhage, Axel A. |
| dc.subject.por.fl_str_mv |
Aspergillus fumigatus NADPH oxidase Calcium signaling Conidial melanin Flotillin Fungal pathogenesis Macrophage Membrane microdomains Phagolysosome vATPase |
| topic |
Aspergillus fumigatus NADPH oxidase Calcium signaling Conidial melanin Flotillin Fungal pathogenesis Macrophage Membrane microdomains Phagolysosome vATPase |
| description |
© 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2021-04-28T14:40:19Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/47593 |
| url |
http://hdl.handle.net/10451/47593 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Cell Rep. 2020 Aug 18;32(7):108017 2211-1247 10.1016/j.celrep.2020.108017 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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