RGD Reference Report - Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera. - Rat Genome Database

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

Authors: Bitar, Aziz  De, Rituparna  Melgar, Silvia  Aung, Kyaw Min  Rahman, Arman  Qadri, Firdausi  Wai, Sun Nyunt  Shirin, Tahmina  Hammarstr├Âm, Marie-Louise 
Citation: Bitar A, etal., PLoS One. 2017 Mar 20;12(3):e0173817. doi: 10.1371/journal.pone.0173817. eCollection 2017.
RGD ID: 25314323
Pubmed: PMID:28319200   (View Abstract at PubMed)
PMCID: PMC5358779   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0173817   (Journal Full-text)

The 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cholera  IEP 25314323miRNA:increased expression:duodenumRGD 
cholera  ISOMIR155 (Homo sapiens)25314323; 25314323miRNA:increased expression:duodenumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir155  (microRNA 155)

Genes (Mus musculus)
Mir155  (microRNA 155)

Genes (Homo sapiens)
MIR155  (microRNA 155)

Additional Information