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 

机构地区：[1]Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China [2]Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Belling 100730, China [3]Department of Critical Care Medicine, Chifeng Hospital, Chifeng, Inner Mongolia 024000, China

出　　处：《Chinese Medical Journal》2016年第14期1704-1710,共7页中华医学杂志（英文版）

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,gilhls.fumigatus 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 A.Jumigatus 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 （rBackground： 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,gilhls.fumigatus 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 A.Jumigatus 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

关 键 词：AspergillusJumigatus lmmunocompromised MTOR Transcription Factor 

分 类 号：S852.4[农业科学—基础兽医学] Q71[农业科学—兽医学]