Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense
Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysacchar...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/224174 |
| Acceso en línea: | http://hdl.handle.net/10261/224174 |
| Access Level: | acceso abierto |
| Palabra clave: | Lipid droplets Mitochondria Innate immunity Immunometabolism Proteomics Antibiotics Cathelicidins |
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España |
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| dc.title.none.fl_str_mv |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense Lipid droplets are innate immune hubs |
| title |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense |
| spellingShingle |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense Bosch, Marta Lipid droplets Mitochondria Innate immunity Immunometabolism Proteomics Antibiotics Cathelicidins |
| title_short |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense |
| title_full |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense |
| title_fullStr |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense |
| title_full_unstemmed |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense |
| title_sort |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense |
| dc.creator.none.fl_str_mv |
Bosch, Marta Sánchez-Álvarez, Miguel Fajardo, Alba Kapetanovic, Ronan Steiner, Bernhard Dutra, Filipe Moreira, Luciana López, Juan Antonio Campo, Rocío Marí, Montserrat Morales-Paytuvi, Frederic Tort, Olivia Gubern, Albert Templin, Rachel M. Curson, James E. B. Martel, Nick Catalá, Cristina Lozano, Francisco Tebar, Francesc Enrich, Carlos Vázquez, Jesús Pozo Barriuso, Miguel Ángel del Sweet, Matthew J. Bozza, Patricia T. Gross, Steven P. Parton, Robert G. Pol, Albert |
| author |
Bosch, Marta |
| author_facet |
Bosch, Marta Sánchez-Álvarez, Miguel Fajardo, Alba Kapetanovic, Ronan Steiner, Bernhard Dutra, Filipe Moreira, Luciana López, Juan Antonio Campo, Rocío Marí, Montserrat Morales-Paytuvi, Frederic Tort, Olivia Gubern, Albert Templin, Rachel M. Curson, James E. B. Martel, Nick Catalá, Cristina Lozano, Francisco Tebar, Francesc Enrich, Carlos Vázquez, Jesús Pozo Barriuso, Miguel Ángel del Sweet, Matthew J. Bozza, Patricia T. Gross, Steven P. Parton, Robert G. Pol, Albert |
| author_role |
author |
| author2 |
Sánchez-Álvarez, Miguel Fajardo, Alba Kapetanovic, Ronan Steiner, Bernhard Dutra, Filipe Moreira, Luciana López, Juan Antonio Campo, Rocío Marí, Montserrat Morales-Paytuvi, Frederic Tort, Olivia Gubern, Albert Templin, Rachel M. Curson, James E. B. Martel, Nick Catalá, Cristina Lozano, Francisco Tebar, Francesc Enrich, Carlos Vázquez, Jesús Pozo Barriuso, Miguel Ángel del Sweet, Matthew J. Bozza, Patricia T. Gross, Steven P. Parton, Robert G. Pol, Albert |
| 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 |
| dc.contributor.none.fl_str_mv |
Fundació La Marató de TV3 Australian Research Council Swiss National Science Foundation National Health and Medical Research Council (Australia) Instituto de Salud Carlos III Ministerio de Ciencia, Innovación y Universidades (España) Agencia Estatal de Investigación (España) Generalitat de Catalunya Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil) Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro Ministerio de Economía y Competitividad (España) Worldwide Cancer Research European Commission Centro Nacional de Investigaciones Cardiovasculares (España) Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Lipid droplets Mitochondria Innate immunity Immunometabolism Proteomics Antibiotics Cathelicidins |
| topic |
Lipid droplets Mitochondria Innate immunity Immunometabolism Proteomics Antibiotics Cathelicidins |
| description |
Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts. Thus, LDs actively participate in mammalian innate immunity at two levels: They are both cell-autonomous organelles that organize and use immune proteins to kill intracellular pathogens as well as central players in the local and systemic metabolic adaptation to infection. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020 2020 2020 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Postprint Postprint info:eu-repo/semantics/acceptedVersion info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/224174 |
| url |
http://hdl.handle.net/10261/224174 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098593-B-I00 RTI2018-098593-B-I00/AEI/10.13039/501100011033 info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2015-67580-P info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-51876-R info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-83130-R SAF2017-83130-R/AEI/10.13039/501100011033 info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SEV-2015-0505 http://dx.doi.org/10.1126/science.aay8085 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
| dc.publisher.none.fl_str_mv |
American Association for the Advancement of Science |
| publisher.none.fl_str_mv |
American Association for the Advancement of Science |
| dc.source.none.fl_str_mv |
reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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| repository.mail.fl_str_mv |
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| _version_ |
1869417324116705280 |
| spelling |
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defenseLipid droplets are innate immune hubsBosch, MartaSánchez-Álvarez, MiguelFajardo, AlbaKapetanovic, RonanSteiner, BernhardDutra, FilipeMoreira, LucianaLópez, Juan AntonioCampo, RocíoMarí, MontserratMorales-Paytuvi, FredericTort, OliviaGubern, AlbertTemplin, Rachel M.Curson, James E. B.Martel, NickCatalá, CristinaLozano, FranciscoTebar, FrancescEnrich, CarlosVázquez, JesúsPozo Barriuso, Miguel Ángel delSweet, Matthew J.Bozza, Patricia T.Gross, Steven P.Parton, Robert G.Pol, AlbertLipid dropletsMitochondriaInnate immunityImmunometabolismProteomicsAntibioticsCathelicidinsLipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts. Thus, LDs actively participate in mammalian innate immunity at two levels: They are both cell-autonomous organelles that organize and use immune proteins to kill intracellular pathogens as well as central players in the local and systemic metabolic adaptation to infection.M.B. acknowledges support from 31/U/2016 from Fundació Marató de TV3. R.K. acknowledges support from an Australian Research Council Discovery Early Career Research Award (DE130100470). B.S. is supported by an Early Postdoc Mobility fellowship from the Swiss National Science Foundation (P2ZHP3_184024). M.J.S. is supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (APP1107914). M.S.-A. was recipient of a CNIC IPP fellowship (COFUND 2014). M.M. is supported by the Instituto de Salud Carlos III (FIS PI19/01410). O.T. is founded by Amgen 2018 Competitive Grant Program. A.P., R.G.P., S.P.G., and P.T.B. have been supported by RGP0020/2015 from the Human Frontier Science Program (HFSP). A.P. is supported by the Ministerio de Ciencia e Innovación (MICINN, RTI2018-098593-B-I00), Fundació Marató de TV3 (31/U/2016), and the CERCA Programme/Generalitat de Catalunya. R.G.P. was supported by the NHMRC of Australia (program grant APP1037320 and Senior Principal Research Fellowship 569452), and the Australian Research Council Centre of Excellence in Convergent Bio-Nanoscience and Technology (CE140100036). P.T.B. is supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil and Fundaçao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ). M.A.D.P. was funded by MICINN (project grants SAF2014-51876-R and SAF2017-83130-R; and IGP-SO grant MINSEV1512-07-2016) and was a Worldwide Cancer Research Foundation grantee (#15-0404). J.V. is supported by MICINN (BIO2015-67580-P) and from the Carlos III Institute of Health-Fondo de Investigación Sanitaria (PRB2, IPT13/0001—ISCIII-SGEFI/FEDER, ProteoRed). The CNIC is supported by the MICINN and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MICINN award SEV-2015-0505).American Association for the Advancement of ScienceFundació La Marató de TV3Australian Research CouncilSwiss National Science FoundationNational Health and Medical Research Council (Australia)Instituto de Salud Carlos IIIMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Generalitat de CatalunyaConselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil)Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de JaneiroMinisterio de Economía y Competitividad (España)Worldwide Cancer ResearchEuropean CommissionCentro Nacional de Investigaciones Cardiovasculares (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501PostprintPostprintinfo:eu-repo/semantics/acceptedVersioninfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/224174reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098593-B-I00RTI2018-098593-B-I00/AEI/10.13039/501100011033info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2015-67580-Pinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-51876-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-83130-RSAF2017-83130-R/AEI/10.13039/501100011033info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SEV-2015-0505http://dx.doi.org/10.1126/science.aay8085Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2241742026-05-22T06:33:51Z |
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15,811543 |