Bacterial ligand of TLR2 signals Stat activation via induction of IRF1/2 and interferon-alpha production

: Liljeroos M, Vuolteenaho R, Rounioja S, Henriques-Normark B, Hallman M, Ojaniemi M

: England

: 2008

: Cellular signalling

: Cell.Signal.

: 20

: 10

: 1873

: 1881

Both type I interferons (IFNs) and interferon regulatory factors (IRFs) are well characterized in viral infections, whereas they are far less studied in bacterially activated toll-like receptor (TLR) pathways. Here, we studied the involvement of IRF1 and IRF2 in TLR2-mediated responses. In mouse macrophages, IRF2 was activated by lipoteichoic acid (LTA) of Staphylococcus aureus, resulting in up-regulation of IRF1 and rapid secretion of IFN-alpha. In addition, LTA-induced activation of Signal transducers and activators of transcription 1 (Stat1) and Stat3 via IRF2. The secretion of IFN-alpha was reduced in IRF2-silenced macrophages, resulting in a disappearance of tyrosine-phosphorylated Stat3 and a reduction of pro-inflammatory responses, despite induction of Mal adapter protein. These results provide a mechanistic insight into the pro-inflammatory responses against S. aureus LTA in mouse macrophages. IRFs can be intersecting factors of viral and bacterial responses in activated TLR signalling pathways.