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白细胞介素-10和干扰素-γ反应中由基因决定的差异与沙眼衣原体小鼠肺炎感染的清除相关。

Genetically determined differences in IL-10 and IFN-gamma responses correlate with clearance of Chlamydia trachomatis mouse pneumonitis infection.

作者信息

Yang X, HayGlass K T, Brunham R C

机构信息

Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.

出版信息

J Immunol. 1996 Jun 1;156(11):4338-44.

PMID:8666805
Abstract

Cytokine patterns elicited by infection are critical in the regulation of the adaptive immune response and in the resolution of infection. Using a murine model of pneumonia induced by intranasal inoculation with the Chlamydia trachomatis mouse pneumonitis (MoPn) biovar, we found that the patterns of immune responses and cytokine production by spleen cells were correlated with quantitative growth of MoPn in the lungs of C57BL/6 and BALB/c mice. Specifically, BALB/c (H-2d) mice had a significantly higher mortality rate and a slower clearance of the organism from the lungs than did C57BL/6 mice (H-2b). BALB/c mice exhibited higher IL-10 production, higher IgG1 Ab responses, and less IFN-gamma production than C57BL/6 mice, which showed higher IFN-gamma production, stronger delayed-type hypersensitivity (DTH) responses, and significantly less IL-10 production. In vivo neutralization of IL-10 in BALB/c mice with an anti-IL-10 mAB during MoPn infection significantly increased the DTH response and enhanced clearance of MoPn. These findings support the hypothesis that excessive IL-10 production in BALB/c mice inhibits Th1-like responses, including IFN-gamma expression and the DTH response following chlamydial infection and consequently delay infection resolution.

摘要

感染引发的细胞因子模式在适应性免疫反应的调节以及感染的消退过程中至关重要。利用鼻内接种沙眼衣原体小鼠肺炎(MoPn)生物变种诱导的小鼠肺炎模型,我们发现C57BL/6和BALB/c小鼠脾脏细胞的免疫反应模式和细胞因子产生与肺部MoPn的定量生长相关。具体而言,BALB/c(H-2d)小鼠的死亡率显著高于C57BL/6小鼠(H-2b),且肺部病原体清除速度较慢。与C57BL/6小鼠相比,BALB/c小鼠表现出更高的IL-10产生、更高的IgG1抗体反应以及更少的IFN-γ产生,而C57BL/6小鼠则表现出更高的IFN-γ产生、更强的迟发型超敏反应(DTH)以及显著更少的IL-10产生。在MoPn感染期间用抗IL-10单克隆抗体在体内中和BALB/c小鼠的IL-10,显著增加了DTH反应并增强了MoPn的清除。这些发现支持了这样的假设,即BALB/c小鼠中过量的IL-10产生会抑制Th1样反应,包括衣原体感染后的IFN-γ表达和DTH反应,从而延迟感染的消退。

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