PMID- 27411458
OWN - NLM
STAT- MEDLINE
DCOM- 20170313
LR  - 20220316
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 129
IP  - 14
DP  - 2016 Jul 20
TI  - mTOR Modulates Lymphocyte Differentiation through T-bet and Eomesodermin in 
      Response to Invasive Pulmonary Aspergillosis in Rats.
PG  - 1704-10
LID - 10.4103/0366-6999.185858 [doi]
AB  - BACKGROUND: Aspergillosis infection is common in the patients with insufficient 
      immunity. The role of mammalian target of rapamycin (mTOR), T-box expressed in 
      T-cells (T-bet), and eomesodermin (EOMES) in mediating T lymphocytes 
      differentiation in response to Aspergillus fumigatus infection in 
      immunocompromised rats was investigated in this study. METHODS: Invasive 
      pulmonary aspergillosis (IPA) of immunosuppressive twenty male rats were 
      established and sacrificed at 24 h (n = 5), 48 h (n = 5), 72 h (n = 5), and 96 h 
      (n = 5) after A. fumigatus infection. In addition, control (n = 5), 
      cyclophosphamide (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 mTOR, 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 of CTX + 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 IPA alone group. Conversely, serum mTOR, 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 
      significantly correlated with EOMES (r = -0.758 and -0.751, respectively, P < 
      0.001). CONCLUSIONS: mTOR may regulate transcription factors of EOMES and T-bet, 
      and by which mechanism, it may modulate lymphocytes differentiation in animals 
      with immune suppression and fungal infection.
FAU - Cui, Na
AU  - Cui N
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 
      100730, China.
FAU - Su, Long-Xiang
AU  - Su LX
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 
      100730, China.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 
      100730, China.
FAU - Xiao, Meng
AU  - Xiao M
AD  - Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking 
      Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, 
      China.
FAU - Yang, Fei
AU  - Yang F
AD  - Department of Critical Care Medicine, Chifeng Hospital, Chifeng, Inner Mongolia 
      024000, China.
FAU - Zheng, Min
AU  - Zheng M
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 
      100730, China.
FAU - Li, Xin
AU  - Li X
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 
      100730, China.
FAU - Xu, Ying-Chun
AU  - Xu YC
AD  - Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking 
      Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, 
      China.
FAU - Liu, Da-Wei
AU  - Liu DW
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 
      100730, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (T-box transcription factor TBX21)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/cytology/metabolism
MH  - Cell Differentiation/genetics/physiology
MH  - Invasive Pulmonary Aspergillosis/*metabolism/pathology
MH  - Lung/metabolism/pathology
MH  - Lymphocytes/*cytology/immunology
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - T-Box Domain Proteins/genetics/*metabolism
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Tissue Culture Techniques
PMC - PMC4960960
EDAT- 2016/07/15 06:00
MHDA- 2017/03/14 06:00
PMCR- 2016/07/20
CRDT- 2016/07/15 06:00
PHST- 2016/07/15 06:00 [entrez]
PHST- 2016/07/15 06:00 [pubmed]
PHST- 2017/03/14 06:00 [medline]
PHST- 2016/07/20 00:00 [pmc-release]
AID - ChinMedJ_2016_129_14_1704_185858 [pii]
AID - CMJ-129-1704 [pii]
AID - 10.4103/0366-6999.185858 [doi]
PST - ppublish
SO  - Chin Med J (Engl). 2016 Jul 20;129(14):1704-10. doi: 10.4103/0366-6999.185858.