Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera

Simple item page
dc.contributor.authorBitar, Aziz
dc.contributor.authorDe, Rituparna
dc.contributor.authorMelgar, Silvia
dc.contributor.authorAung, Kyaw Min
dc.contributor.authorRahman, Arman
dc.contributor.authorQadri, Firdausi
dc.contributor.authorWai, Sun Nyunt
dc.contributor.authorShirin, Tahmina
dc.contributor.authorHammarström, Marie-Louise
dc.contributor.funderSeventh Framework Programme
dc.contributor.funderInternational Centre for Diarrhoeal Disease Research, Bangladesh
dc.contributor.funderStyrelsen för Internationellt Utvecklingssamarbete
dc.contributor.funderSwedish Research Council-Natural and Engineering Sciences
dc.contributor.funderUmeå Universitet
dc.contributor.funderKempestiftelserna
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderCounty of Västerbotten
dc.contributor.funderInternational Centre for Diarrhoeal Disease Research, Bangladesh
dc.date.accessioned2017-06-20T11:39:44Z
dc.date.available2017-06-20T11:39:44Z
dc.date.issued2017-03-20
dc.description.abstractThe potential immunomodulatory role of microRNAs in small intestine of patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) infection was investigated. Duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. Levels of miR-146a, miR-155 and miR-375 and target gene (IRAK1, TRAF6, CARD10) and 11 cytokine mRNAs were determined by qRT-PCR. The cellular source of microRNAs in biopsies was analyzed by in situ hybridization. The ability of V. cholerae bacteria and their secreted products to cause changes in microRNA- and mRNA levels in polarized tight monolayers of intestinal epithelial cells was investigated. miR-146a and miR 155 were expressed at significantly elevated levels at acute stage of V. cholerae infection and declined to normal at convalescent stage (P<0.009 versus controls; P = 0.03 versus convalescent stage, pairwise). Both microRNAs were mainly expressed in the epithelium. Only marginal down-regulation of target genes IRAK1 and CARD10 was seen and a weak cytokine-profile was identified in the acute infected mucosa. No elevation of microRNA levels was seen in ETEC infection. Challenge of tight monolayers with the wild type V. cholerae O1 strain C6706 and clinical isolates from two study-participants, caused significant increase in miR-155 and miR-146a by the strain C6706 (P<0.01). One clinical isolate caused reduction in IRAK1 levels (P<0.05) and none of the strains induced inflammatory cytokines. In contrast, secreted factors from these strains caused markedly increased levels of IL-8, IL-1?, and CARD10 (P<0.001), without inducing microRNA expression. Thus, miR-146a and miR- 155 are expressed in the duodenal epithelium at the acute stage of cholera. The inducer is probably the V. cholerae bacterium. By inducing microRNAs the bacterium can limit the innate immune response of the host, including inflammation evoked by its own secreted factors, thereby decreasing the risk of being eliminated.en
dc.description.sponsorshipSwedish International Development Cooperation Agency (grant INT-ICDDR,B-HN-01-AV); Swedish Research Council-Natural and Engineering Sciences (grant no. 2013-4522; grant no. 2014-4401); Umeå University (Fund for Biotechnology-oriented Basic Science; Fund of Donations to the Medical Faculty); Kempe Foundations (grant no. SMK-1454); Science Foundation Ireland (grant no. SFI/12/RC/2273); County of Västerbotten (combined medical practice- and research fellowship)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide0173817
dc.identifier.citationBitar, A., De, R., Melgar, S., Aung, K. M., Rahman, A., Qadri, F., Wai, S. N., Shirin, T. and Hammarström, M.-L. (2017) 'Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera', PLoS ONE, 12(3), e0173817 (20pp). doi: 10.1371/journal.pone.0173817en
dc.identifier.doi10.1371/journal.pone.0173817
dc.identifier.endpage20
dc.identifier.issn1932-6203
dc.identifier.issued3
dc.identifier.journaltitlePLOS ONEen
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/4105
dc.identifier.volume12
dc.language.isoenen
dc.publisherPLoSen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/222720/EU/Molecular Targets Open for Regulation by the gut flora – New Avenues for improved Diet to Optimize European health/TORNADO
dc.relation.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173817
dc.rights© 2017, Bitar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectMicroRNAsen
dc.subjectmiR-146aen
dc.subjectmiR-155en
dc.subjectVibrio choleraeen
dc.subjectDuodenal epitheliumen
dc.subjectSmall intestineen
dc.titleInduction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of choleraen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
2749.pdf
Size:
1.85 MB
Format:
Adobe Portable Document Format
Description:
Published Version
Download
Collections
APC Microbiome Ireland - Journal Articles