Staphylococcal enterotoxin B in vivo modulates both gamma interferon receptor expression and ligand-induced activation of signal transducer and activator of transcription 1 in T cells.
Superantigens (SAg) are bacterial exotoxins that provoke extreme responses in the immune system; for example, the acute hyperactivation of SAg-reactive T cells that leads to toxic shock syndrome is followed within days by strong immunosuppression. The gamma interferon (IFN-gamma) response is deeply affected in both extremes. The implication of IFN-gamma in the pathophysiology of lethal shock induced in mice after a secondary challenge with the SAg staphylococcal enterotoxin B (SEB) prompted us to study the regulation of IFN-gamma secretion and the intracellular response. We demonstrate in this study that a rechallenge with SEB becomes lethal only when given inside a critical time window after SEB priming and is associated with an increase of IFN-gamma serum release 72 h after priming. However, at this time, a selective blockade of IFN-gamma/STAT1 signaling develops in spleen cells, correlating with a lack of expression of the IFN-gamma receptor beta subunit and STAT1 in the T-cell population. Selective blockade of the STAT1 signaling pathway--while simultaneously maintaining STAT3 signaling and expression--may be a protective mechanism that shortens IFN-gamma production during the Th1 effector response. This blockade may also have consequences on switching towards a suppressor phenotype with chronic exposure to the superantigen.
Plaza
R
R
Department of Immunology, Hospital de la Santa Creu i Sant Pau, Avda. Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
Rodriguez-Sanchez
J L
JL
Juarez
C
C
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D024202:Electrophoretic Mobility Shift Assay; D004768:Enterotoxins / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017471:Receptors, Interferon / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000276:immunology / Q000378:metabolism*; D012772:Shock, Septic / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D000096743:Interferon gamma Receptor
D000942:Antigens, Bacterial; D004768:Enterotoxins; D007371:Interferon-gamma; D008024:Ligands; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D018089:Superantigens; D000096743:Interferon gamma Receptor; C494080:Stat1 protein, mouse; C031818:enterotoxin B, staphylococcal