Unknown,Transcriptomics,Genomics,Proteomics

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Global analysis of miRNA expression profile during Mycobacterium tuberculosis infection of human primary dendritic cells

ABSTRACT: Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens in human history and remains the second leading cause of death from an infectious agent worldwide. The major reason of Mtb success principally relies on its ability to perfectly adapt to the host, by establishing latent infection and evading from the control driven by immune system. Accordingly, both innate and adaptive immune responses are required to control TB progression and pathogenesis and in particular dendritic cells (DC), as professional antigen presenting cells, are one of the major cellular effectors of the anti-mycobacterial response. In this context, we performed a microarray analysis to characterize the de-regulation of cellular miRNAs during Mtb infection of human DC. Human DC were prepared from human peripheral blood mononuclear cells of anonymous healthy blood donors and infected with Mtb for 3, 8 and 24 hours. This data set contains the global miRNA expression profiling in uninfected and Mtb-infected DC cultures to identify altered signature of miRNAs potentially implicated in Mtb-mediated immune evasion strategies.

ORGANISM(S): Homo sapiens

SUBMITTER: Angela Grassi

PROVIDER: E-MTAB-6083 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 2,3-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype. In summary, regulatory myeloid DC and macrophages may play a dual role during life-threatening granulomatous infections, such as tuberculosis: on one hand, regulatory myeloid cells promote pathogen containment by efficiently killing intracellular bacteria, on the other hand these cells inhibit granuloma-associated T cells and thereby might be involved in the retention of TNF-controlled granuloma integrity protecting the host from granuloma break-down and pathogen dissemination. Experiment Overall Design: Transcriptional profiles of immature mo-DC (immDC, n=3), mature stimulatory mo-DC (matDC, n=3) and mature inhibitory mo-DC either stimulated with prostaglandin E2 (PGE2-DC, n=3) or infected with L.monocytogenes (infDC, n=3) were compared on Affymetrix HG-U133A platform. All samples represent biological replicates and were processed separately throughout the experiment.

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Global analysis of miRNA expression profile during Mycobacterium tuberculosis infection of human primary dendritic cells

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