Impact of interferon-γ receptor deficiency on experimental Staphylococcus aureus septicemia and arthritis

Abstract

The role of IFN-γ in the regulation of host resistance of Staphylococcus aureus was studied using IFN-γ receptor-deficient (IFN-γ R-/-) mice in a model of S. aureus-induced septicemia and arthritis. IFN-γ R-/- mice and wild-type controls were inoculated intravenously with a toxic shock syndrome toxin-1-producing S. aureus LS-1 strain. IFN-γ 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-γ 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-γ 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 β and TNF-beta mRNA expression. Thus, bacterial growth and proinflammatory cytokines IL-1 β, TNF-beta, and IL-6 were higher at the early stage of infection in IFN-γ-/- mice but increased at the later stage in wild-type littermates. Our data indicate that the absence of IFN-γ 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.