Aspergillus fumigatus induces microRNA-155 expression in vitro in human monocyte-derived dendritic cells

MicroRNAs (miRNA) are a class of post-transcriptional regulators which are short, approximately 22 nucleotide RNA sequences that bind to complementary sequences in the 3´UTR of multiple target mRNAs, usually resulting in their silencing and/or degradation.

This study shows that the post-transcriptional regulator miR155 is significantly up-regulated in human monocyte-derived dendritic cells (moDCs) upon ex vivo infection with the pathogenic mould Aspergillus fumigatus. MoDCs showed a time-dependent increase of the expression of miR155 after stimulation. We revealed that the induction of miR155 depends on the morphology of the mould.

In addition, miR155 expression was dependent on the MOI. We could demonstrate that a higher MOI triggered stronger increases in miR155 expression over time. The induction averaged from 2.9 fold (MOI=1) to 4.9 fold (MOI=2.5) to 14-fold (MOI=5).

Finally, we revealed that monocytes did not respond with an increased expression of miR155 to co-cultivation with A. fumigatus. However, stimulation of monocytes with LPS led to a rise in miR155 levels.

Our study describes that A. fumigatus induces increased levels of miR146a and miR155 in moDCs. It is obvious that functional studies have to follow to define specific target pathways and to identify additional relevant miRNA. Improving our understanding on the role of miRNA and their target genes controlling inflammatory cytokine expression might lead to the development of new therapeutic interventions for IA.