AUTHOR=Mannala Gopala K. , Izar Benjamin , Rupp Oliver , Schultze Tilman , Goesmann Alexander , Chakraborty Trinad , Hain Torsten 

TITLE=Listeria monocytogenes Induces a Virulence-Dependent microRNA Signature That Regulates the Immune Response in Galleria mellonella

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02463

DOI=10.3389/fmicb.2017.02463

ISSN=1664-302X

ABSTRACT=<p>microRNAs (miRNAs) coordinate several physiological and pathological processes by regulating the fate of mRNAs. Studies conducted <italic>in vitro</italic> indicate a role of microRNAs in the control of host-microbe interactions. However, there is limited understanding of miRNA functions in <italic>in vivo</italic> models of bacterial infections. In this study, we systematically explored changes in miRNA expression levels of <italic>Galleria mellonella</italic> larvae (greater-wax moth), a model system that recapitulates the vertebrate innate immunity, following infection with <italic>L. monocytogenes</italic>. Using an insect-specific miRNA microarray with more than 2000 probes, we found differential expression of 90 miRNAs (39 upregulated and 51 downregulated) in response to infection with <italic>L. monocytogenes</italic>. We validated the expression of a subset of miRNAs which have mammalian homologs of known or predicted function. In contrast, non-pathogenic <italic>L. innocua</italic> failed to induce these miRNAs, indicating a virulence-dependent miRNA deregulation. To predict miRNA targets using established algorithms, we generated a publically available <italic>G. mellonella</italic> transcriptome database. We identified miRNA targets involved in innate immunity, signal transduction and autophagy, including spätzle, MAP kinase, and optineurin, respectively, which exhibited a virulence-specific differential expression. Finally, <italic>in silico</italic> estimation of minimum free energy of miRNA-mRNA duplexes of validated microRNAs and target transcripts revealed a regulatory network of the host immune response to <italic>L. monocytogenes</italic>. In conclusion, this study provides evidence for a role of miRNAs in the regulation of the innate immune response following bacterial infection in a simple, rapid and scalable <italic>in vivo</italic> model that may predict host-microbe interactions in higher vertebrates.</p>