The role of STAT1 in viral sensitization to LPS.
The phenomenon of endotoxin sensitization by virus infection is well documented but not yet well understood. Infection by virtually any viral agent will quickly induce expression of type I interferons (IFN-alpha/beta), and type II IFN-gamma production will follow as NK cells and T cells are activated. It has been well established that type II IFN pretreatment can intensify the effects of endotoxin. We have recently demonstrated that type I IFN induction by lymphocytic choriomeningitis virus (LCMV) infection dramatically increases TNF-alpha production following LPS treatment, and that this sensitization by type I IFN is STAT1 dependent. Taken together these data suggest that the STAT1-mediated, MyD88-independent, arm of the LPS signaling pathway plays an important role in endotoxin toxicity, and that this pathway mediates a major component of virus-enhanced LPS sensitization.
Department of Pediatrics, Columbus Children's Research Institute, The Ohio State University Columbus, Ohio 43205, USA. durbinj@pediatrics.ohio-state.edu
Joan
J
Durbin
Leslie
L
Doughty
Ken
K
Nguyen
Michael
M
Caligiuri
Jeff
J
Van Deusen
Christine
C
Biron
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha