IFN-γ上调Th17/IL-17应答介导衣原体呼吸道感染免疫保护

目的 探讨IFN-γ在小鼠沙眼衣原体感染中对Th17/IL-17应答的调节作用.方法 利用沙眼衣原体鼠肺炎株小鼠呼吸道感染模型,用抗鼠IFN-γ单克隆抗体吸入中和肺组织IFN-γ,对照组给予同等剂量的独特型抗体IgG2a,于感染后7 d处死小鼠.免疫酶法检测小鼠肺组织衣原体生长;利用RT-PCR技术检测衣原体感染小鼠肺组织中Th17相关因子IL-17及其上游因子IL-23 mRNA的表达;细胞内细胞因子染色检测衣原体感染小鼠脾脏IL-17-CD4+T细胞的扩增.结果 与对照组相比,IFN-γ抗体中和小鼠有严重的疾病状态,包括明显的体重下降、肺组织更高的衣原体负荷和肺组织更严重的病理损伤;肺组织IL-17和IL-23 mRNA的表达水平显著降低;脾脏IL-17-CD4+T细胞百分率也显著降低.结论 小鼠衣原体感染中,IFN-γ通过上调Th17/IL-17应答起保护作用.

Abstract：

Objective To investigate the regulation of IFN-γ to Th17 response in Chlamydia muridarum (Cm) lung infection in mice. Methods A murine model of pneumonia induced by intranasal inoculation of Cm was used for this study. Anti-mouse IFN-γ McAbs were used to neutralize endogenous IFN-γfollowing Cm lung infection. Control group received the same dose of isotype antibody (IgG2a). Mice were sacrificed at day 7 postinfection. Chlamydial growth in the lung was assessed by immunoenzyme technique.IL-17 and IL-23 mRNA expression in the lung was assayed by RT-PCR and the proliferation of IL-17 + CD4 +T cells in the spleen was assayed by intracellular cytokine staining. Results IFN-γ-neutralized mice exhibited serious disease course, include greater body weight loss, higher organism growth and much more severe pathological changes in the lung compared with control mice. The mRNA expression of IL-17 and IL-23 in the lung and the proliferation of IL-17 + CD4 + T cells in the spleen significantly decreased in the IL-17- neutralized mice. Conclusion IFN-γ was protective in Cm lung infection through up-regulating the antigen specific Th17 responses.

IFN-γup-regulates Th17/IL-17 response against Chlamydia trachomatis lung infection

Objective To investigate the regulation of IFN-γ to Th17 response in Chlamydia muridarum (Cm) lung infection in mice. Methods A murine model of pneumonia induced by intranasal inoculation of Cm was used for this study. Anti-mouse IFN-γ McAbs were used to neutralize endogenous IFN-γfollowing Cm lung infection. Control group received the same dose of isotype antibody (IgG2a). Mice were sacrificed at day 7 postinfection. Chlamydial growth in the lung was assessed by immunoenzyme technique.IL-17 and IL-23 mRNA expression in the lung was assayed by RT-PCR and the proliferation of IL-17 + CD4 +T cells in the spleen was assayed by intracellular cytokine staining. Results IFN-γ-neutralized mice exhibited serious disease course, include greater body weight loss, higher organism growth and much more severe pathological changes in the lung compared with control mice. The mRNA expression of IL-17 and IL-23 in the lung and the proliferation of IL-17 + CD4 + T cells in the spleen significantly decreased in the IL-17- neutralized mice. Conclusion IFN-γ was protective in Cm lung infection through up-regulating the antigen specific Th17 responses.