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2011-05-24Zeitschriftenartikel DOI: 10.1371/journal.pone.0020258
Integrated MicroRNA-mRNA-Analysis of Human Monocyte Derived Macrophages upon Mycobacterium avium subsp. hominissuis Infection
dc.contributor.authorSharbati, Jutta
dc.contributor.authorLewin, Astrid
dc.contributor.authorKutz-Lohroff, Barbara
dc.contributor.authorKamal, Elisabeth
dc.contributor.authorEinspanier, Ralf
dc.contributor.authorSharbati, Soroush
dc.date.accessioned2018-05-07T14:36:59Z
dc.date.available2018-05-07T14:36:59Z
dc.date.created2011-05-30
dc.date.issued2011-05-24none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/reJL5Td9KB9w/PDF/288SJzVPSOVTE.pdf
dc.identifier.urihttp://edoc.rki.de/176904/878
dc.description.abstractBackground: Many efforts have been made to understand basal mechanisms of mycobacterial infections. Macrophages are the first line of host immune defence to encounter and eradicate mycobacteria. Pathogenic species have evolved different mechanisms to evade host response, e.g. by influencing macrophage apoptotic pathways. However, the underlying molecular regulation is not fully understood. A new layer of eukaryotic regulation of gene expression is constituted by microRNAs. Therefore, we present a comprehensive study for identification of these key regulators and their targets in the context of host macrophage response to mycobacterial infections. Methodology/Principal Findings: We performed microRNA as well as mRNA expression analysis of human monocyte derived macrophages infected with several Mycobacterium avium hominissuis strains by means of microarrays as well as quantitative reverse transcription PCR (qRT-PCR). The data revealed the ability of all strains to inhibit apoptosis by transcriptional regulation of BCL2 family members. Accordingly, at 48 h after infection macrophages infected with all M. avium strains showed significantly decreased caspase 3 and 7 activities compared to the controls. Expression of let-7e, miR- 29a and miR-886-5p were increased in response to mycobacterial infection at 48 h. The integrated analysis of microRNA and mRNA expression as well as target prediction pointed out regulative networks identifying caspase 3 and 7 as potential targets of let-7e and miR-29a, respectively. Consecutive reporter assays verified the regulation of caspase 3 and 7 by these microRNAs. Conclusions/Significance: We show for the first time that mycobacterial infection of human macrophages causes a specific microRNA response. We furthermore outlined a regulatory network of potential interactions between microRNAs and mRNAs. This study provides a theoretical concept for unveiling how distinct mycobacteria could manipulate host cell response. In addition, functional relevance was confirmed by uncovering the control of major caspases 3 and 7 by let-7e and miR-29a, respectively.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectHumanseng
dc.subjectOligonucleotide Array Sequence Analysiseng
dc.subjectMacrophages/microbiologyeng
dc.subjectCells Culturedeng
dc.subject3' Untranslated Regions/geneticseng
dc.subjectMacrophages/metabolismeng
dc.subjectMicroRNAs/geneticseng
dc.subjectMycobacterium avium/physiologyeng
dc.subjectRNA Messenger/geneticseng
dc.subjectTuberculosis/geneticseng
dc.subjectTuberculosis/microbiologyeng
dc.subject.ddc610 Medizin
dc.titleIntegrated MicroRNA-mRNA-Analysis of Human Monocyte Derived Macrophages upon Mycobacterium avium subsp. hominissuis Infection
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10014306
dc.identifier.doi10.1371/journal.pone.0020258
dc.identifier.doihttp://dx.doi.org/10.25646/803
local.edoc.container-titlePLoS ONE
local.edoc.container-textSharbati J, Lewin A, Kutz-Lohroff B, Kamal E, Einspanier R, et al. (2011) Integrated MicroRNA-mRNA-Analysis of Human Monocyte Derived Macrophages upon Mycobacterium avium subsp. hominissuis Infection. PLoS ONE 6(5): e20258. doi:10.1371/journal.pone.0020258
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0020258
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume6
local.edoc.container-issue5
local.edoc.container-year2011

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