mTOR Modulates Lymphocyte Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis in Rats

作     者：Na Cui Long-Xiang Su Hao Wang Meng Xiao Fei Yang Min Zheng Xin Li Ying-Chun Xu Da-Wei Liu Cui Na;Su Long-Xiang;Wang Hao;Xiao Meng;Yang Fei;Zheng Min;Li Xin;Xu Ying-Chun;Liu Da-Wei

作者机构：Department of Critical Care Medicine Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100730 China Department of Clinical Laboratory Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences Belling 100730 China Department of Critical Care Medicine Chifeng Hospital Chifeng Inner Mongolia 024000 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2016年第129卷第14期

页      面：1704-1710页

核心收录：

学科分类：0710[理学-生物学] 090602[农学-预防兽医学] 071010[理学-生物化学与分子生物学] 07[理学] 09[农学] 0906[农学-兽医学] 

基　　金：supported by the Beijing Municipal Natural Science Foundation Special Project Funds for Clinical Research of Chinese Medical Association 

主　　题：AspergillusJumigatus lmmunocompromised mTOR Transcription Factor 

摘      要：Background： Aspergillosis infection is common in the patients with insufficient immunity. The role of mammalian target of rapamycin （roTOR）, T-box expressed in T-cells （T-bet）, and eomesodermin （EOMES） in mediating T lymphocytes differentiation in response to Aspep,*** infection in immunocompromised rats was investigated in this study. Methods： lnvasive pulmonary aspergillosis （IPA） ofimmunosuppressive twenty male rats were established and sacrificed at 24 h （n = 5）, 48 h （n = 5）, 72 11 （n = 5）, and 96 h （n = 5） atter *** infection. In addition, control （n = 5）, cyclophospharnide （CTX） （n = 5）, and aspergillosis （n = 5） group were also established the tissues and pathology of lung tissue was examined by hematoxylin and eosin staining. CD8＋ T-cells was sorted by flow cytometry. Serum roTOR, S6K, T-bet, and EOMES were quantified by enzyme-linked immunosorbent assay. Results： Histology of lung tissue indicated severe lung tissue injury including infiltration of inflammatory cells, alveolar wall damage or degradation, blood congestion, and hemorrhage in the CTX, IPA, and CTX ＋ IPA rats. Hyphae were seen in the IPA, and CTX ＋ IPA groups. The proportion of CD8^＋ T-cells was significantly increased in the animals ofCTX ＋ IPA. Memory CD8＋ T-cells was significantly increased in early stage （24 h and 48 h, P 〈 0.001）, but decreased in the late phase of fungal infection （72 h and 96 h） in the animals of CTX ＋ IPA. In addition, at early stage of fungal infection （24 h and 48 h）, serum mTOR （P 〈 0.001 ）, S6K （P 〈 0.001 ）, and T-bet （P 〈 0.05） was significantly higher, while EOMES was significantly lower （P 〈 0.001 ）, in CTX ＋ IPA group than that in control, CTX alone or 1PA alone group. Conversely, serum roTOR, S6K, T-bet, and EOMES showed opposite changed in the late stage （72 h and 96 h）. Pearson＇s correlation analysis indicated that mTOR and S6K were significantly correlated with T-bet （r = 0.901 and 0.91, respectively, P 〈 0.001 ）, but negatively and sig