Journal article

Publication year: 2017

Journal: PLoS ONE

Volume number: 12

Issue number: 4

ISSN: 1932-6203

Open access status: Gold

DOI Link: https://doi.org/10.1371/journal.pone.0176204

Publisher: Public Library of Science

Abstract: 

Background

Legionella pneumophila (L. pneumophila) is a causative agent of severe pneumonia. It is highly adapted to intracellular replication and manipulates host cell functions like vesicle trafficking and mRNA translation to its own advantage. However, it is still unknown to what extent microRNAs (miRNAs) are involved in the Legionella-host cell interaction.

Methods

WT and MyD88(-/-) murine bone marrow-derived macrophages (BMM) were infected with L. pneumophila, the transcriptome was analyzed by high throughput qPCR array (microRNAs) and conventional qPCR (mRNAs), and mRNA-miRNA interaction was validated by luciferase assays with 3-UTR mutations and western blot.

Results

L. pneumophila infection caused a pro-inflammatory reaction and significant miRNA changes in murine macrophages. In MyD88(-/-) cells, induction of inflammatory markers, such as Ccxl1/Kc, Il6 and miR-146a-5p was reduced. Induction of miR-125a-3p was completely abrogated in MyD88(-/-) cells. Target prediction analyses revealed N-terminal asparagine amidase 1 (NTAN1), a factor from the n-end rule pathway, to be a putative target of miR125a-3p. This interaction could be confirmed by luciferase assay and western blot.

Conclusion

Taken together, we characterized the miRNA regulation in L. pneumophila infection with regard to MyD88 signaling and identified NTAN1 as a target of miR-125a-3p. This finding unravels a yet unknown feature of Legionella-host cell interaction, potentially relevant for new treatment options.

Harvard Citation style: Jentho, E., Bodden, M., Schulz, C., Jung, A., Seidel, K., Schmeck, B., et al. (2017) microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection and targets NTAN1, PLoS ONE, 12(4), Article e0176204. https://doi.org/10.1371/journal.pone.0176204

APA Citation style: Jentho, E., Bodden, M., Schulz, C., Jung, A., Seidel, K., Schmeck, B., & Bertrams, W. (2017). microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection and targets NTAN1. PLoS ONE. 12(4), Article e0176204. https://doi.org/10.1371/journal.pone.0176204