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Genetic deficiency of NOD2 confers resistance to invasive aspergillosis

2018Journal article Open access
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dc.contributor.authorGresnigt, Mark S.
dc.contributor.authorCunha, Cristina
dc.contributor.authorJaeger, Martin
dc.contributor.authorGonçalves, Samuel M.
dc.contributor.authorMalireddi, R. K. Subbarao
dc.contributor.authorAmmerdorffer, Anne
dc.contributor.authorLubbers, Rosalie
dc.contributor.authorOosting, Marije
dc.contributor.authorRasid, Orhan
dc.contributor.authorJouvion, Grégory
dc.contributor.authorFitting, Catherine
dc.contributor.authorJong, Dirk J. de
dc.contributor.authorLacerda, João
dc.contributor.authorCampos, António
dc.contributor.authorMelchers, Willem J. G.
dc.contributor.authorLagrou, Katrien
dc.contributor.authorMaertens, Johan
dc.contributor.authorKanneganti, Thirumala-Devi
dc.contributor.authorCarvalho, Agostinho
dc.contributor.authorIbrahim-Granet, Oumaima
dc.contributor.authorvan de Veerdonk, Frank L.
dc.date.accessioned2022-11-22T15:51:57Z
dc.date.available2022-11-22T15:51:57Z
dc.date.issued2018
dc.description© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractInvasive aspergillosis (IA) is a severe infection that can occur in severely immunocompromised patients. Efficient immune recognition of Aspergillus is crucial to protect against infection, and previous studies suggested a role for NOD2 in this process. However, thorough investigation of the impact of NOD2 on susceptibility to aspergillosis is lacking. Common genetic variations in NOD2 has been associated with Crohn's disease and here we investigated the influence of these genetic variations on the anti-Aspergillus host response. A NOD2 polymorphism reduced the risk of IA after hematopoietic stem-cell transplantation. Mechanistically, absence of NOD2 in monocytes and macrophages increases phagocytosis leading to enhanced fungal killing, conversely, NOD2 activation reduces the antifungal potential of these cells. Crucially, Nod2 deficiency results in resistance to Aspergillus infection in an in vivo model of pulmonary aspergillosis. Collectively, our data demonstrate that genetic deficiency of NOD2 plays a protective role during Aspergillus infection.pt_PT
dc.description.sponsorshipF.L.v.d.V. was supported by the E-rare project EURO-CMC. M.O. was supported by the NWO, 016.176.006). A.C. and C.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 the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to A.C. and SFRH/BPD/96176/2013 to C.C.).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Commun. 2018 Jul 6;9(1):2636pt_PT
dc.identifier.doi10.1038/s41467-018-04912-3pt_PT
dc.identifier.eissn2041-1723
dc.identifier.urihttp://hdl.handle.net/10451/55210
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationIF/00735/2014pt_PT
dc.relationTHE ROLE OF INFLAMMASOME ACTIVATION IN HOST IMMUNITY TO FUNGAL INFECTION - The inflammasome-microbiota interplay in antifungal immunity
dc.relation.publisherversionhttps://www.nature.com/ncomms/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleGenetic deficiency of NOD2 confers resistance to invasive aspergillosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTHE ROLE OF INFLAMMASOME ACTIVATION IN HOST IMMUNITY TO FUNGAL INFECTION - The inflammasome-microbiota interplay in antifungal immunity
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F96176%2F2013/PT
oaire.citation.issue1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume9pt_PT
person.familyNameLacerda
person.givenNameJoão
person.identifier559297
person.identifier.ciencia-id6412-2B63-2364
person.identifier.orcid0000-0003-1351-2809
person.identifier.scopus-author-id6603819609
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationafb302b1-8272-48de-b347-cb5b54a0a3da
relation.isAuthorOfPublication.latestForDiscoveryafb302b1-8272-48de-b347-cb5b54a0a3da
relation.isProjectOfPublicationf53289b8-69d0-42bb-b3a1-e7533a1d0951
relation.isProjectOfPublication.latestForDiscoveryf53289b8-69d0-42bb-b3a1-e7533a1d0951

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