小鼠沙眼衣原体肺感染过程中Treg细胞与Th17反应关系  

Relationship between CD4+CD25+Foxp3+ regulatory T cells and Th17 responses in Chlamydia muridarum pulmonary infection

作　　者：周晓静[1] 陈丽香[2] 周望展[1] 黄君[1] 刘丹慧[1] 周文江[2] 胡芸文[2] 吕建新[1] 周晓辉[2] 

机构地区：[1]温州医学院,浙江省医学遗传学重点实验室,温州325035 [2]上海市(复旦大学附属)公共卫生临床中心,上海201500

出　　处：《微生物学报》2013年第1期74-81,共8页Acta Microbiologica Sinica

基　　金：国家自然科学基金(31270217);上海市自然科学基金(12ZR1426400);浙江省自然科学基金(Y2081073)~~

摘　　要：【目的】对沙眼衣原体在BALB/c小鼠肺部感染过程中CD4+CD25+Foxp3+调节性T细胞(regulatory T cells,Treg)与Th17反应关系进行初步探讨。【方法】取6-8周龄的BALB/c小鼠,鼻腔吸入25μL含5×103IFU的沙眼衣原体鼠肺炎菌株(Chlamydia muridarum,Cm),建立沙眼衣原体小鼠肺感染模型。监测感染后不同时期小鼠体重变化;检测肺组织衣原体包涵体形成单位(IFU)及肺组织病理改变;利用流式细胞术检测Cm感染后小鼠体内Treg细胞百分率;ELISA检测肺组织上清液IL-6、TGF-β、IL-17、IL-2细胞因子的的表达;qRT-PCR检测KC(keratinocyte derived chemokine)mRNA和MIP-2(macrophage inflammatory protein-2)mRNA的表达差异。【结果】用5xl03IFU Cm经鼻腔吸入感染后小鼠发生沙眼衣原体肺炎,表现为体重下降、肺组织大量炎症细胞浸润并可检测到衣原体繁殖。Cm感染后第3天,小鼠体内Treg细胞占CD4+T细胞的百分比明显降,随后开始恢复,第7天恢复原来水平,一直持续到衣原体清除。TGF-β、IL-2的表达与Treg细胞动态变化一致。与Th17相关细胞因子IL-6、IL-17和Th17相关趋化因子KC、MIP-2的表达于第3天开始升高,至第7天达到最高水平,随后逐渐减少。【结论】在衣原体感染BALB/c小鼠过程中,Treg可能通过提供TGF-β并在IL-6帮助下促进Th17应答产生。[ Objective] To study the relationship between CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells and Thl7 responses during pulmonary infection of Chlamydia muridarum （Cm） in BALB/c mice. [ Methods ] BALB/e mice aged 6 - 8 weeks were inoculated intranasally with 5 x 103 IFU of Cm to set up the murine model of Chlamydial pneumonia. The body weight changes, the growth of Cm and the pathology in the lung were monitored at different time post-infection. To determine the CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells responses in BALB/c mice, intracellular cytokine staining was used to assay the percentage of CD4 ＋ CD25 ＋ Foxp3 ＋ T cells in the spleen and mediastinum lymph node （MLN）. The production of cytokines/chemokines in the lung were monitored, including IL-6,TGF-beta,IL-17,IL-2 （by ELISA）, KC and MIP-2 （by RT-PCR）. [Results] Intranasally infected with 5 × 10^3 IFU of Cm in mice resulted in chlamydial pneumonitis featured by body Weight lost, chlamydia growth and pathological damage in the lung compared with their uninfected counterparts. On day 3 post-infection, the percentage of CD4 ＋ CD25 ＋ Foxp3 ＋ T cells in the spleen and MLN were significantly decreased than the control mice; then began to increase and recover to the original level on day 7 post- infection. The production of Thl7 associated cytokines/chemokines such as IL-6, IL-17, KCand MIP-2 increased, which peaked on day 7 post-infection, then gradually reduced. The production of TGF-beta and IL-2 was consistent with the trend of CD4 ＋ CD25 ＋ Foxp3 ＋ T cells. [ Conclusion] During pulmonary infection of Cm in BALB/c mice, CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells may promote type 17 T cell immunity through providing TGF-beta in the presence of IL- 6.

关 键 词：沙眼衣原体鼠肺炎菌株 CD4+CD25+Foxp3+调节性T细胞 TH17 

分 类 号：R363[医药卫生—病理学]