Beatty W L, Byrne G I, Morrison R P
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison 53706.
Proc Natl Acad Sci U S A. 1993 May 1;90(9):3998-4002. doi: 10.1073/pnas.90.9.3998.
An in vitro cell culture system was used to study the effect of interferon gamma (IFN-gamma) on Chlamydia trachomatis growth and differentiation. The effect of IFN-gamma on chlamydiae was dose-dependent. IFN-gamma at 2 ng/ml completely inhibited chlamydial growth and differentiation; however, persistent infection was established when chlamydiae were cultured with IFN-gamma at 0.2 ng/ml. Persistent infection was characterized by the development of noninfectious atypical chlamydial forms from which infectious progeny could be recovered only when IFN-gamma was removed from the culture system. Analysis of persistently infected cells by immunofluorescent microscopy and immunoblotting with specific antibodies revealed that the atypical chlamydial forms had near-normal levels of the 60-kDa heat shock protein, an immunopathologic antigen, and a paucity of the major outer membrane protein, a protective antigen. Furthermore, steady-state levels of other outer membrane constituents, such as the 60-kDa cysteine-rich outer membrane protein and lipopolysaccharide, were greatly reduced. If IFN-gamma causes similar events to occur in vivo, then persistently infected cells could augment the pathogenesis of the chronic inflammatory sequelae that follow chlamydial infection by serving as depots of antigen capable of stimulating a sustained inflammatory response.
采用体外细胞培养系统研究γ干扰素(IFN-γ)对沙眼衣原体生长和分化的影响。IFN-γ对衣原体的作用呈剂量依赖性。2 ng/ml的IFN-γ可完全抑制衣原体的生长和分化;然而,当衣原体与0.2 ng/ml的IFN-γ一起培养时,会形成持续性感染。持续性感染的特征是出现无感染性的非典型衣原体形态,只有当从培养系统中去除IFN-γ后,才能从中回收有感染性的子代。通过免疫荧光显微镜和用特异性抗体进行免疫印迹分析持续感染的细胞,结果显示非典型衣原体形态中免疫病理抗原60-kDa热休克蛋白的水平接近正常,而保护性抗原主要外膜蛋白的水平较低。此外,其他外膜成分如60-kDa富含半胱氨酸的外膜蛋白和脂多糖的稳态水平也大大降低。如果IFN-γ在体内引起类似事件发生,那么持续感染的细胞可能会作为能够刺激持续炎症反应的抗原库,从而加剧衣原体感染后慢性炎症后遗症的发病机制。