Legionella pneumophila-Derived Outer Membrane Vesicles Promote Bacterial Replication in Macrophages

• DOI: 10.1371/journal.ppat.1005592
• Publication Date: 2016-04-22T17:38:18Z
• Authors: Anna Lena Jung; Cornelia Stoiber; Christina E. Herkt; Christine Schulz; Wilhelm Bertrams; Bernd Schmeck
• Keywords: Legionella

The formation and release of outer membrane vesicles (OMVs) is a phenomenon Gram-negative bacteria. This includes Legionella pneumophila (L. pneumophila), causative agent severe pneumonia. Upon its transmission into the lung, L. primarily infects replicates within macrophages. Here, we analyzed influence OMVs on To this end, differentiated THP-1 cells were incubated with increasing doses OMVs, leading to TLR2-dependent classical activation macrophages pro-inflammatory cytokines. Inhibition TLR2 NF-κB signaling reduced induction Furthermore, treatment prior infection replication in cells. Blocking or heat denaturation restored bacterial first 24 h infection. With prolonged infection-time, OMV pre-treated became more permissive for than untreated showed increased numbers Legionella-containing vacuoles cytokine induction. Additionally, miRNA-146a was found be transcriptionally induced by facilitate replication. Accordingly, IRAK-1, one miRNA-146a's targets, activation-dependent degradation, which rendered In conclusion, are initially potent stimulators macrophages, acting via TLR2, NF-κB, while at later time points, miR-146a-dependent IRAK-1 suppression. might thereby promote spreading host.