Zhao Y X, Tarkowski A
Department of Clinical Immunology, University of Gteborg, Sweden.
J Immunol. 1995 Dec 15;155(12):5736-42.
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.
在金黄色葡萄球菌诱导的败血症和关节炎模型中，使用干扰素-γ受体缺陷（IFN-γR-/-）小鼠研究了干扰素-γ在调节宿主对金黄色葡萄球菌抵抗力中的作用。IFN-γR-/-小鼠和野生型对照小鼠静脉注射产中毒性休克综合征毒素-1的金黄色葡萄球菌LS-1菌株。在整个感染过程中，与野生型同窝小鼠相比，IFN-γR-/-小鼠出现关节炎的频率明显更高且病情更严重（p<0.01）。值得注意的是，IFN-γR-/-小鼠在接种葡萄球菌后早期就发展为严重败血症，死亡率很高。然而，与IFN-γR-/-小鼠相比，野生型小鼠在疾病后期的死亡率显著更高（p<0.05）。败血症相关死亡率的这种差异结果与血液和实质器官中细菌清除的缺陷有关，并且与血清IL-6水平、脾脏IL-1β和TNF-βmRNA表达密切相关。因此，在IFN-γ-/-小鼠感染早期细菌生长和促炎细胞因子IL-1β、TNF-β和IL-6较高，但在野生型同窝小鼠后期增加。我们的数据表明，IFN-γR的缺失在金黄色葡萄球菌感染中会产生有害和有益的影响，这取决于疾病阶段和感染部位。
