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Resveratrol therapeutics combines both antimicrobial and immunomodulatory properties against respiratory infection by nontypeable Haemophilus influenzae

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dc.contributor.authorEuba, Begoña
dc.contributor.authorLópez López, Nahikari
dc.contributor.authorRodríguez Arce, Irene
dc.contributor.authorFernández Calvet, Ariadna
dc.contributor.authorBarberán, Montserrat
dc.contributor.authorCaturla, Nuria
dc.contributor.authorMartí, Sara
dc.contributor.authorDíez Martínez, Roberto
dc.contributor.authorGarmendia García, Juncal
dc.contributor.departmentIdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutuaes_ES
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.contributor.funderUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoaes
dc.date.accessioned2018-09-19T09:37:42Z
dc.date.available2018-09-19T09:37:42Z
dc.date.issued2017
dc.description.abstractThe respiratory pathogen nontypeable Haemophilus influenzae (NTHi) is an important cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) that requires efficient treatments. A previous screening for host genes differentially expressed upon NTHi infection identified sirtuin-1, which encodes a NAD-dependent deacetylase protective against emphysema and is activated by resveratrol. This polyphenol concomitantly reduces NTHi viability, therefore highlighting its therapeutic potential against NTHi infection at the COPD airway. In this study, resveratrol antimicrobial effect on NTHi was shown to be bacteriostatic and did not induce resistance development in vitro. Analysis of modulatory properties on the NTHi-host airway epithelial interplay showed that resveratrol modulates bacterial invasion but not subcellular location, reduces inflammation without targeting phosphodiesterase 4B gene expression, and dampens β defensin-2 gene expression in infected cells. Moreover, resveratrol therapeutics against NTHi was evaluated in vivo on mouse respiratory and zebrafish septicemia infection model systems, showing to decrease NTHi viability in a dose-dependent manner and reduce airway inflammation upon infection, and to have a significant bacterial clearing effect without signs of host toxicity, respectively. This study presents resveratrol as a therapeutic of particular translational significance due to the attractiveness of targeting both infection and overactive inflammation at the COPD airway.en
dc.description.sponsorshipN.L.L. was funded by a contract from Department of Economy, Regional Govern from Navarra, Spain, reference 0011–1307; I.R.A. is funded by a PhD studentship from Universidad Pública de Navarra, Spain. This work has been funded by grants from MINECO SAF2012-31166 and SAF2015-66520-R, Health Department, Regional Govern from Navarra, Spain, reference 3/2016, and SEPAR 31/2015 to J.G.en
dc.format.extent14 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.1038/s41598-017-13034-7
dc.identifier.issn2045-2322 (Electronic)
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/30720
dc.language.isoengen
dc.publisherSpringer Natureen
dc.relation.ispartofScientific Reports, 7: 12860en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//SAF2012-31166/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//SAF2015-66520-R/ES/en
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-017-13034-7
dc.rights© The Author(s) 2017. 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.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHaemophilus influenzae (NTHi)en
dc.subjectResveratrolen
dc.titleResveratrol therapeutics combines both antimicrobial and immunomodulatory properties against respiratory infection by nontypeable Haemophilus influenzaeen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dspace.entity.typePublication
relation.isAuthorOfPublication9fc7a317-1022-4fd5-b6ae-5a3065d960c1
relation.isAuthorOfPublication94ad1041-7e91-4171-9452-f4e270bd5dee
relation.isAuthorOfPublicationeab5adde-437b-46f6-9496-2fa2b16b308f
relation.isAuthorOfPublication.latestForDiscovery9fc7a317-1022-4fd5-b6ae-5a3065d960c1

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