摘要
目的观察AIM2（absent in melanoma2）在感染早期识别胞浆小鼠巨细胞病毒（MCMV）DNA的变化状况。方法建立MCMV全身播散型感染模型，接种MCMVSmith株后第1、3、5和7天各处死3只小鼠；同时设模拟感染小鼠作为正常对照。Western blot检测脾脏巨噬细胞中AIM2、衔接子凋亡相关点样蛋白（ASC）和caspase-1蛋白的表达状况；同时应用ELISA法检测血清中IL-1β和IL-18的水平；空斑法测定感染小鼠唾液腺感染性病毒滴度。结果MCMV感染后第3、5、7天，小鼠唾液腺组织中感染性病毒滴度逐渐增加；MCMV感染鼠脾脏巨噬细胞中AIM2、ASC和caspase-1蛋白的表达呈现一致的变化，与模拟感染对照鼠比较，AIM2、ASC和caspase-1蛋白相对吸光值在感染后第1天开始升高（P〉0．05），第3天明显升高并达峰值[分别为（1．121±0．243）vs（0．240±0．046），（1．318±0．333）VS（0．248±0．090），（1．085±0．243）VS（0．247±0．064）；P〈0．01]，其后接近正常；MCMV感染鼠血清IL-1β和IL-18水平在感染后第3天也明显高于模拟感染对照鼠[分别为（112．72±5．20）pg／ml VS（47．86±4．35）pg／ml，（42．74±4．23）pg／ml VS（22．60±2．82）pg／ml；P〈0．01]，其后均逐渐下降接近正常。结论MCMC感染早期巨噬细胞通过AIM2炎性体识别胞浆MCMVDNA，可能成为CMV感染及感染后所引起的疾病的治疗靶点。
Objective To observe the changes of AIM2 （absent in melanoma 2） inflammasome during early murine cytomegalovirus （MCMV） infection. Methods BALB/c mice were randomly divided into two groups. One was infected with MCMV Smith for establishing disseminated infection, the other was sham-inoculated control. On days l, 3, 5 and 7 of the experiment, three mice of each group were randomly chosen to be killed separately. The expression of AIM2, ASC and caspase-1 in splenic macrophages was detected by Western blot, the levels of IL-1 [3 and IL-18 in sera were measured by double antibody sandwich ELISA , and the viral titers in salivary gland tissues were quantified by a standard plaque assay . Results The MCMV titers in salivary gland tissues were gradually increased in MCMV-infected mice on days 3,5 and 7, while the expressions of AIM2 in macrophages were began to increase on day 1 and significantly increased and reached the highest level on day 3 but gradually decreased afterwards. The relative intensity of AIM2 on day 3 differed significantly between the MCMV-infected mice and the controls （1. 121±0. 243 vs 0. 240±0.046, P〈0.01, t test）, as did ASC （ 1. 318±0.333 vs 0. 248±0. 090, P〈0.01 ） and caspase-1 （ 1. 085± 0. 243 vs 0. 247±0, 064, P〈0.01 ）. Meanwhile, the levels of IL-1β and IL-18 in MCMV-infected mice were （112.72±5.20） pg/ml and （ 42.74±4.23 ） pg/ml, and the levels were significantly higher （ P〈0.01 ） than those in controls [ （47.86±4.35） pg/ml and （22.60±2.82） pg/ml]. Conclusion These results demonstrate that AIM2 inflammasome is activated in macrophages during early MCMV infection and could be as a therapeutic target for CMV-induced diseases.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2012年第1期31-35,共5页
Chinese Journal of Microbiology and Immunology
基金
教育部博士点基金资助项目（20090142110076）
