Fachbereich Veterinärmedizin



    Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection (2011)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Sharbati, Jutta (WE 3)
    Lewin, Astrid
    Kutz-Lohroff, Barbara (WE 3)
    Kamal, Elisabeth
    Einspanier, Ralf (WE 3)
    Sharbati, Soroush (WE 3)
    SFB 852-TP B04: Untersuchungen zum Einfluss von intestinalen Faktoren wie Zink oder Mikroorganismen auf regulierende mircoRNA und Charakterisierung d. nachgeschalteten Reaktionsmechanismen
    PLoS one; 6(5) — S. e20258
    ISSN: 1932-6203
    URL (Volltext): http://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000016063
    DOI: 10.1371/journal.pone.0020258
    Pubmed: 21629653
    Institut für Veterinär-Biochemie

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    Abstract / Zusammenfassung

    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.

    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.

    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.