Impact of interferon-gamma receptor deficiency on experimental Staphylococcus aureus septicemia and arthritis.
The role of IFN-gamma in the regulation of host resistance of Staphylococcus aureus was studied using IFN-gamma receptor-deficient (IFN-gamma R-/-) mice in a model of S. aureus-induced septicemia and arthritis. IFN-gamma R-/- mice and wild-type controls were inoculated intravenously with a toxic shock syndrome toxin-1-producing S. aureus LS-1 strain. IFN-gamma R-/- mice displayed significantly more frequent and more severe arthritis compared with wild-type littermates (p < 0.01) throughout the course of infection. Notably, IFN-gamma R-/- mice developed severe sepsis with high mortality early after the inoculation with staphylococci. However, the mortality of wild-type mice became significantly higher at later stages of the disease compared with IFN-gamma R-/- mice (p < 0.05). This differential outcome of sepsis-related mortality was associated with deficiencies of bacterial elimination from blood and parenchymatous organs and correlated well to serum levels of IL-6 and spleen IL-1 beta and TNF-beta mRNA expression. Thus, bacterial growth and proinflammatory cytokines IL-1 beta, TNF-beta, and IL-6 were higher at the early stage of infection in IFN-gamma-/- mice but increased at the later stage in wild-type littermates. Our data indicate that the absence of IFN-gamma R leads to harmful as well as beneficial effects in S. aureus infection, depending on the stage of the disease and the localization of the infection.
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001170:Arthritis, Infectious / Q000382:microbiology* / Q000473:pathology; D016470:Bacteremia / Q000382:microbiology* / Q000473:pathology; D001427:Bacterial Toxins; D002455:Cell Division; D004768:Enterotoxins / Q000096:biosynthesis; D005260:Female; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D013211:Staphylococcus aureus; D018089:Superantigens; D000096743:Interferon gamma Receptor
D000907:Antibodies, Bacterial; D015703:Antigens, CD; D001427:Bacterial Toxins; D004768:Enterotoxins; D007371:Interferon-gamma; D017471:Receptors, Interferon; D018089:Superantigens; D000096743:Interferon gamma Receptor; C030107:enterotoxin F, Staphylococcal