The mammalian microRNA response to bacterial infections

Institute for Molecular Infection Biology (IMIB) and Research Centre for Infection Diseases (ZINF), University of Würzburg
RNA biology (Impact Factor: 4.97). 06/2012; 9(6):742-50. DOI: 10.4161/rna.20018
Source: PubMed


MicroRNAs are small RNAs that post-transcriptionally regulate eukaryotic gene expression. In addition to their involvement in a wide range of physiological and pathological processes, including viral infections, microRNAs are increasingly implicated in the eukaryotic response to bacterial pathogens. Recent studies have characterized changes in host microRNA expression following infection with exclusively extracellular (Helicobacter pylori) or intracellular (Salmonella enterica) Gram-negative bacteria, as well as in the response to Gram-positive (Listeria monocytogenes) and other pathogens (Mycobacterium and Francisella species). In this review, we discuss the emerging roles of microRNAs in mammalian host signaling and defense against bacterial pathogens.

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    • "MiRNAs have also been shown to play crucial roles during infection by diverse pathogens, including viruses, parasites and bacteria (reviewed in [13] [14] [15]). Seminal work on the role of miRNAs in hostpathogen interactions focused on virus infections. "
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    ABSTRACT: MicroRNAs are small non-coding RNAs with a central role in the post-transcriptional control of gene expression, that have been implicated in a wide-range of biological processes. Regulation of miRNA expression is increasingly recognized as a crucial part of the host response to infection by bacterial pathogens, as well as a novel molecular strategy exploited by bacteria to manipulate host cell pathways. Here, we review the current knowledge of bacterial pathogens that modulate host microRNA expression, focusing on mammalian host cells, and the implications of microRNAs (miRNA) regulation on the outcome of infection. The emerging role of commensal bacteria, as part of the gut microbiota, on host miRNA expression in the presence or absence of bacterial pathogens is also discussed.
    FEBS Letters 08/2014; 588(22). DOI:10.1016/j.febslet.2014.08.002 · 3.17 Impact Factor
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    • "It has recently been reported that miRNAs can sense biotic stresses operating as an integral part of host immune responses to microbial infections, caused by viral, bacterial and Apicomplexan pathogens [22–24]. Interestingly, in A. gambiae the upstream control regions of the major components of miRNA biogenesis, Drosha, Dcr-1 and Ago-1 are enriched in the potential binding sites for NF-kappaB-related transcription factors [10], presumably providing a link between the miRNA pathway and immune responses. "
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    ABSTRACT: Background: microRNAs (miRNAs) are a highly abundant class of small noncoding regulatory RNAs that post-transcriptionally regulate gene expression in multicellular organisms. miRNAs are involved in a wide range of biological and physiological processes, including the regulation of host immune responses to microbial infections. Small-scale studies of miRNA expression in the malaria mosquito Anopheles gambiae have been reported, however no comprehensive analysis of miRNAs has been performed so far. Results: Using small RNA sequencing, we characterized de novo A. gambiae miRNA repertoire expressed in adult sugar- and blood-fed females. We provided transcriptional evidences for 123 miRNAs, including 58 newly identified miRNAs. Out of the newly described miRNAs, 19 miRNAs are homologs to known miRNAs in other insect species and 17 miRNAs share sequence similarity restricted to the seed sequence. The remaining 21 novel miRNAs displayed no obvious sequence homology with known miRNAs. Detailed bioinformatics analysis of the mature miRNAs revealed a sequence variation occurring at their 5'-end and leading to functional seed shifting in more than 5% of miRNAs. We also detected significant sequence heterogeneity at the 3'-ends of the mature miRNAs, mostly due to imprecise processing and post-transcriptional modifications. Comparative analysis of arm-switching events revealed the existence of species-specific production of dominant mature miRNAs induced by blood feeding in mosquitoes. We also identified new conserved and fragmented miRNA clusters and A. gambiae-specific miRNA gene duplication. Using miRNA expression profiling, we identified the differentially expressed miRNAs at an early time point after regular blood feeding and after infection with the rodent malaria parasite Plasmodium berghei. Significant changes were detected in the expression levels of 4 miRNAs in blood-fed mosquitoes, whereas 6 miRNAs were significantly upregulated after P. berghei infection. Conclusions: In the current study, we performed the first systematic analysis of miRNAs in A. gambiae. We provided new insights on mature miRNA sequence diversity and functional shifts in the mosquito miRNA evolution. We identified a set of the differentially expressed miRNAs that respond to normal and infectious blood meals. The extended set of Anopheles miRNAs and their isoforms provides a basis for further experimental studies of miRNA expression patterns and biological functions in A. gambiae.
    BMC Genomics 07/2014; 15(1):557. DOI:10.1186/1471-2164-15-557 · 3.99 Impact Factor
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    • "SHIP1 has also been shown to attenuate Ras activity by binding Shc (Damen et al., 1996). MicroRNAs (miRs) are post-transcriptional regulators of gene expression and Francisella has developed methods to use microRNAs to its advantage (Cremer et al., 2009; Eulalio et al., 2012). Specifically, miR-155, which targets the 3′ UTR of SHIP1, is induced by F. novicida but not Schu S4, resulting in higher levels of SHIP1 with Schu S4 (Cremer et al., 2009). "
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    ABSTRACT: Francisella tularensis can bypass and suppress host immune responses, even to the point of manipulating immune cell phenotypes and intercellular inflammatory networks. Strengthening these responses such that immune cells more readily identify and destroy the bacteria is likely to become a viable (and perhaps necessary) strategy for combating infections with Francisella, especially given the likelihood of antibiotic resistance in the foreseeable future. Monocytes and macrophages offer a niche wherein Francisella can invade and replicate, resulting in substantially higher bacterial load that can overcome the host. As such, understanding their responses to Francisella may uncover potential avenues of therapy that could promote a lowering of bacterial burden and clearance of infection. These response pathways include Toll-like Receptor 2 (TLR2), the caspase-1 inflammasome, Interferons, NADPH oxidase, Phosphatidylinositide 3-kinase (PI3K), and the Ras pathway. In this review we summarize the literature pertaining to the roles of these pathways during Francisella infection, with an emphasis on monocyte/macrophage responses. The therapeutic targeting of one or more such pathways may ultimately become a valuable tool for the treatment of tularemia, and several possibilities are discussed.
    Frontiers in Cellular and Infection Microbiology 02/2014; 4:18. DOI:10.3389/fcimb.2014.00018 · 3.72 Impact Factor
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