Abstract：
IFN-gamma is a key cytokine controlling Brucella infection, and the diverse functions of this cytokine are mediated by IFN regulatory factors (IRFs) such as IRF-1, IRF-2, and IFN consensus sequence binding protein (ICSBP). However, the roles of these three IRFs in Brucella infection have not been investigated. The infection of each IRF-deficient mouse strain provides an opportunity to determine not only the significance of each IRF molecule but also the crucial immune components necessary for host defense during in vivo infection, because respective IRF-deficient mouse strains contain unique immunodeficient phenotypes. Brucella abortus S2308-infected IRF-1-/- mice were dead within 2 wk postinfection, while IRF-2-/- mice contained less splenic Brucella CFU than wild-type mice at the early stage of infection. Infected ICSBP-/- mice maintained a plateau of splenic Brucella CFU throughout the infection. Additional infection of IL-12p40-, NO synthase 2-, and gp91(phox)-deficient mice indicates that these immune components are crucial for Brucella immunity and may contribute to the susceptibility of IRF-1-/- and ICSBP-/- mice. Immunologic and histopathological analyses of infected IRF-1-/- mice indicate that the absence of IL-12p40 induction and serious hepatic damage are involved in the death of IRF-1-/- mice. These results indicate that 1) IRF-1 and ICSBP are essential transcriptional factors for IFN-gamma-mediated protection against Brucella; 2) IL-12, reactive nitrogen intermediates, and reactive oxygen intermediates are crucial immune components against Brucella, and their absence may contribute to the susceptibility of IRF-1-/- and ICSBP-/- mice; and 3) hepatic damage caused by Brucella virulence contributes to the death of IRF-1-/- mice.
摘要：
IFN-γ是控制布鲁氏菌感染的关键细胞因子，这种细胞因子的多种功能是由IFN调节因子（IRF）介导的，例如IRF-1，IRF-2和IFN共有序列结合蛋白（ICSBP）。然而,这三种IRF在布鲁氏菌感染中的作用尚未研究。每个IRF缺陷小鼠品系的感染提供了一个机会，不仅可以确定每个IRF分子的重要性，还可以确定体内感染期间宿主防御所需的关键免疫成分。因为各个IRF缺陷小鼠品系含有独特的免疫缺陷表型。流产布鲁氏菌S2308感染的IRF-1-/-小鼠在感染后2周内死亡，而IRF-2-/-小鼠在感染早期的脾布鲁氏菌CFU含量低于野生型小鼠。感染的ICSBP-/-小鼠在整个感染过程中维持了脾布鲁氏菌CFU的平台。IL-12p40-的额外感染，NO合酶2-,和gp91（phox）缺陷小鼠表明这些免疫成分对布氏杆菌免疫至关重要，可能有助于IRF-1-/-和ICSBP-/-小鼠的易感性。感染的IRF-1-/-小鼠的免疫和组织病理学分析表明，IRF-1-/-小鼠的死亡涉及IL-12p40诱导的缺乏和严重的肝损伤。这些结果表明，1）IRF-1和ICSBP是IFN-γ介导的针对布鲁氏菌的保护作用的必需转录因子；2）IL-12，反应性氮中间体，活性氧中间体是对抗布鲁氏菌的重要免疫成分，它们的缺失可能导致IRF-1-/-和ICSBP-/-小鼠的易感性；3）布鲁氏菌毒力引起的肝损伤有助于IRF-1-/-小鼠的死亡。
