Bacterial ligand of TLR2 signals Stat activation via induction of IRF1/2 and interferon-alpha production.
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.
Liljeroos
Mari
M
Institute of Clinical Medicine, Division of Pediatrics, University of Oulu, Oulu, FIN-90014, Finland.
Vuolteenaho
Reetta
R
Rounioja
Samuli
S
Henriques-Normark
Birgitta
B
Hallman
Mikko
M
Ojaniemi
Marja
M
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D002460:Cell Line; D007249:Inflammation; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D050836:Interferon Regulatory Factor-2 / Q000378:metabolism*; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013211:Staphylococcus aureus / Q000737:chemistry*; D013682:Teichoic Acids / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D008024:Ligands; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D050791:STAT Transcription Factors; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D014157:Transcription Factors; C009900:lipoteichoic acid; D016899:Interferon-beta; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase