Resveratrol therapeutics combines both antimicrobial and immunomodulatory properties against respiratory infection by nontypeable Haemophilus influenzae
Resumen: The 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 ß 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.
Idioma: Inglés
DOI: 10.1038/s41598-017-13034-7
Año: 2017
Publicado en: Scientific reports 7, 1 (2017), 12860 [14 pp]
ISSN: 2045-2322

Factor impacto JCR: 4.122 (2017)
Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 12 / 64 = 0.188 (2017) - Q1 - T1
Factor impacto SCIMAGO: 1.533 - Multidisciplinary (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2012-31166
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2015-66520-R
Tipo y forma: Article (Published version)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)

Creative Commons You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.


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