Peng Ying, Gao Xiaoling, Yang Jie, Shekhar Sudhanshu, Wang Shuhe, Fan Yijun, Zhao Weiming, Yang Xi
Departments of Medical Microbiology and Immunology, University of Manitoba, Winnipeg, Manitoba, Canada Department of Medical Microbiology, Shandong University School of Medicine, Jinan, Shandong, PR China.
Departments of Medical Microbiology and Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
Mol Med. 2014 Mar 20;20(1):109-19. doi: 10.2119/molmed.2013.00115.
The role of interleukin-22 (IL-22) in intracellular bacterial infections is a controversial issue, although the contribution of this cytokine to host defense against extracellular bacterial pathogens has been well established. In this study, we focused on an intra-cellular bacterium, Chlamydia, and evaluated the production and function of IL-22 in host defense against chlamydial lung infection using a mouse model. We found that Chlamydia muridarum infection elicited quick IL-22 responses in the lung, which increased during infection and were reduced when bacterial loads decreased. More importantly, blockade of endogenous IL-22 using neutralizing anti-IL-22 monoclonal antibodies (mAb) resulted in more severe disease in the mice, leading to significantly higher weight loss and bacterial growth and much more severe pathological changes than treatment with isotype control antibody. Immunological analyses identified significantly lower T helper 1 (Th1) and Th17 responses in the IL-22-neutralized mice. In contrast, intranasal administration of exogenous IL-22 significantly enhanced protection following chlamydial lung infection, which was associated with a significant increase of Th17 response. The data demonstrate that IL-22 is a critical cytokine, mediating host defense against chlamydial lung infection and coordinating the function of distinct Th-cell subsets, particularly Th1 and Th17, in the process.
白细胞介素-22（IL-22）在细胞内细菌感染中的作用是一个有争议的问题，尽管这种细胞因子对宿主抵御细胞外细菌病原体的贡献已得到充分证实。在本研究中，我们聚焦于一种细胞内细菌——衣原体，并使用小鼠模型评估了IL-22在宿主抵御衣原体肺部感染中的产生及功能。我们发现，鼠衣原体感染在肺部引发了快速的IL-22反应，该反应在感染期间增加，而当细菌载量下降时则降低。更重要的是，使用中和抗IL-22单克隆抗体（mAb）阻断内源性IL-22会导致小鼠病情更严重，体重减轻和细菌生长显著增加，且病理变化比用同型对照抗体治疗时更严重。免疫学分析表明，IL-22中和的小鼠中T辅助细胞1（Th1）和Th17反应显著降低。相反，鼻内给予外源性IL-22可显著增强衣原体肺部感染后的保护作用，这与Th17反应的显著增加有关。数据表明，IL-22是一种关键的细胞因子，介导宿主抵御衣原体肺部感染，并在此过程中协调不同Th细胞亚群（特别是Th1和Th17）的功能。
