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Host and microbiota interactions are critical for development of murine Crohn’s-like ileitis

2016-05Journal article Restricted access
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dc.contributor.authorRoulis, M
dc.contributor.authorBongers, G
dc.contributor.authorArmaka, M
dc.contributor.authorSalviano, T
dc.contributor.authorHe, Z
dc.contributor.authorSingh, A
dc.contributor.authorSeidler, U
dc.contributor.authorBecker, C
dc.contributor.authorDemengeot, J
dc.contributor.authorFurtado, G C
dc.contributor.authorLira, S A
dc.contributor.authorKollias, G
dc.date.accessioned2018-03-02T16:47:26Z
dc.date.available2018-03-02T16:47:26Z
dc.date.issued2016-05
dc.descriptionThis deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027991/pt_PT
dc.descriptionThis publication hasn't any creative commons license associated.pt_PT
dc.description.abstractDeregulation of host-microbiota interactions in the gut is a pivotal characteristic of Crohn's disease. It remains unclear, however, whether commensals and/or the dysbiotic microbiota associated with pathology in humans are causally involved in Crohn's pathogenesis. Here, we show that Crohn's-like ileitis in Tnf(ΔARE/+) mice is microbiota-dependent. Germ-free Tnf(ΔARE/+) mice are disease-free and the microbiota and its innate recognition through Myd88 are indispensable for tumor necrosis factor (TNF) overexpression and disease initiation in this model. The epithelium of diseased mice shows no major defects in mucus barrier and paracellular permeability. However, Tnf(ΔARE/+) ileitis associates with the reduction of lysozyme-expressing Paneth cells, mediated by adaptive immune effectors. Furthermore, we show that established but not early ileitis in Tnf(ΔARE/+) mice involves defective expression of antimicrobials and dysbiosis, characterized by Firmicutes expansion, including epithelial-attaching segmented filamentous bacteria, and decreased abundance of Bacteroidetes. Microbiota modulation by antibiotic treatment at an early disease stage rescues ileitis. Our results suggest that the indigenous microbiota is sufficient to drive TNF overexpression and Crohn's ileitis in the genetically susceptible Tnf(ΔARE/+) hosts, whereas dysbiosis in this model results from disease-associated alterations including loss of lysozyme-expressing Paneth cells.pt_PT
dc.description.sponsorshipERC project MCs-inTEST grant: (340217); Innovative Medicines Initiative project BeTheCure (115142-2); NIH grant: (P01 DK072201); CCFA research grant (#330239); EC FP7 funded project INFRAFRONTIER-I3: (312325); Gulbenkian Institute; Deutsche Forschungsgemeinschaft grants: (SPP1656, SFB 796, KFO 257 CEDER); Sonderforschungsbereich grants: (SFB 621/C9, DFG grant SE460/13-4); InfrafrontierGR Infrastructure grants: (ERDF, NSRF 2007–2013).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMucosal Immunology volume 9, pages 787–797 (2016) doi:10.1038/mi.2015.102pt_PT
dc.identifier.doi10.1038/mi.2015.102pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/845
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relationP01 DK072201pt_PT
dc.relationMesenchymal Cells of the Lamina Propria in Intestinal Epithelial and Immunological Homeostasis.
dc.relationBeTheCuRE
dc.relationSPP1656pt_PT
dc.relationSFB 796pt_PT
dc.relationDevelopment of mouse mutant resources for functional analyses of human diseases - Enhancing the translation of research into innovation
dc.relationSFB 621/C9pt_PT
dc.relationDFG grant SE460/13-4pt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/mi2015102pt_PT
dc.subjectAnimalspt_PT
dc.subjectCells, Culturedpt_PT
dc.subjectCrohn Diseasept_PT
dc.subjectDisease Models, Animalpt_PT
dc.subjectDysbiosispt_PT
dc.subjectGastrointestinal Microbiomept_PT
dc.subjectHost-Pathogen Interactionspt_PT
dc.subjectHumanspt_PT
dc.subjectIleitispt_PT
dc.subjectIntestinal Mucosapt_PT
dc.subjectMicept_PT
dc.subjectMice, Inbred C57BLpt_PT
dc.subjectMice, Knockoutpt_PT
dc.subjectMyeloid Differentiation Factor 88pt_PT
dc.subjectTumor Necrosis Factor-alphapt_PT
dc.titleHost and microbiota interactions are critical for development of murine Crohn’s-like ileitispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMesenchymal Cells of the Lamina Propria in Intestinal Epithelial and Immunological Homeostasis.
oaire.awardTitleBeTheCuRE
oaire.awardTitleDevelopment of mouse mutant resources for functional analyses of human diseases - Enhancing the translation of research into innovation
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/340217/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/115142/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/312325/EU
oaire.citation.endPage797pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage787pt_PT
oaire.citation.titleMucosal Immunologypt_PT
oaire.citation.volume9pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamFP7
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication9f3e54b6-aaa1-427c-859b-3a8e98935720
relation.isProjectOfPublication76d5b98b-151d-46ca-8588-84a946c681f0
relation.isProjectOfPublicationc8305e81-2896-48ab-8ae3-470d257dfdd0
relation.isProjectOfPublication.latestForDiscovery9f3e54b6-aaa1-427c-859b-3a8e98935720

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