J Infect Dis. 2016 Mar 16. pii: jiw109. [Epub ahead of print]
Streptococcus pneumoniae causes high mortality as a major pneumonia-inducing pathogen. In pneumonia, control of innate immunity is necessary to prevent organ damage. We assessed the role of microRNAs as regulators in pneumococcus infection of human macrophages.Exposure of primary blood-derived human macrophages with pneumococci resulted in transcriptional changes in several gene clusters and a significant deregulation of 10 microRNAs. Computational network analysis retrieved miRNA-146a as one putatively important regulator of pneumococci-induced host cell activation. Its induction partly depended on bacterial viability and was completely inhibited by blocking toll-like receptor 2 (TLR-2) or depleting its mediator MyD88. Furthermore, miRNA-146a induction did not require the autocrine feedback of IL-1β and TNF-α released from infected macrophages, and repressed the TLR-2 downstream mediators IRAK-1 and TRAF-6 as well as the inflammatory factors cyclooxygenase 2 and IL-1β. In summary, pneumococci recognition induces a negative feedback loop, preventing excessive inflammation via miR-146a and potentially other miRNAs.
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PMID: 26984146 [PubMed - as supplied by publisher]