Brown Charles R, Blaho Victoria A, Fritsche Kevin L, Loiacono Christie M
Department of Molecular Microbiology, Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
J Interferon Cytokine Res. 2006 Jun;26(6):390-9. doi: 10.1089/jir.2006.26.390.
Activation of the transcription factor Stat1 by interferon-gamma (IFN-gamma) is an important step in the development of antimicrobial effector mechanisms against many bacterial pathogens. Susceptibility to murine Lyme arthritis has been correlated with the production of several proinflammatory cytokines, especially IFN-gamma. To determine the role of IFN-mediated effector mechanisms in the development of Lyme borreliosis, we infected Stat1-deficient mice on both resistant (DBA), and susceptible (C3H) genetic backgrounds. Arthritis in Stat1(/) mice was similar to that of wild-type controls in both mouse strains. Spirochete loads in tissues were also unchanged in Stat1(/) mice. C3H Stat1(/) mice exhibited increased inflammation in the heart, whereas carditis was unchanged in DBA Stat1(/) mice. These results demonstrate that inhibition of macrophage activation and responses to IFN-gamma-mediated signaling do not alter the arthritis resistance or susceptibility phenotype; however, they do affect the severity of carditis in susceptible mouse strains.
γ-干扰素（IFN-γ）激活转录因子Stat1是针对许多细菌病原体的抗菌效应机制发展中的重要一步。对小鼠莱姆关节炎的易感性与几种促炎细胞因子的产生相关，尤其是IFN-γ。为了确定IFN介导的效应机制在莱姆病发展中的作用，我们在抗性（DBA）和易感（C3H）遗传背景下感染了Stat1缺陷小鼠。Stat1（/）小鼠的关节炎在两种小鼠品系中均与野生型对照相似。Stat1（/）小鼠组织中的螺旋体载量也未改变。C3H Stat1（/）小鼠心脏炎症增加，而DBA Stat1（/）小鼠的心肌炎未改变。这些结果表明，抑制巨噬细胞活化和对IFN-γ介导信号的反应不会改变关节炎抗性或易感性表型；然而，它们确实会影响易感小鼠品系中心肌炎的严重程度。
