PMID- 32431684
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231103
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 11
DP  - 2020
TI  - T-Bet Expression Mediated by the mTOR Pathway Influences CD4(+) T Cell Count in 
      Mice With Lethal Candida Sepsis.
PG  - 835
LID - 10.3389/fmicb.2020.00835 [doi]
LID - 835
AB  - The sustained high morbidity and mortality of Candida sepsis are mainly caused by 
      compromise of host immunity. Clinically, it is often manifested as a significant 
      decrease in CD4(+) T cell count, although the mechanism is unclear. We 
      established a lethal mice Candida sepsis model and used Murine Sepsis Score to 
      group mice with different disease severity to establish the influence of T-bet 
      expression on CD4(+) T cell count in Candida sepsis. We found that CD4(+) T cell 
      count decreased in Candida-infected compared to uninfected mice, and the degree 
      of decrease increased with aggravation of sepsis. Expression of T-bet similarly 
      decreased with worsening of sepsis, but it was significantly enhanced in 
      candidiasis in comparison of naive state. To clarify its possible mechanism, we 
      measured the activity of mammalian target of rapamycin (mTOR), which is a key 
      regulator of T-bet expression. The mTOR pathway was activated after infection and 
      its activity increased with progression of sepsis. We used mice with 
      T-cell-specific knockout of mTOR or tuberous sclerosis complex (TSC)1 to further 
      inhibit or strengthen the mTOR signaling pathway. We found that mTOR deletion 
      mice had a higher CD4(+) T cell count by regulating T-bet expression, and the 
      result in TSC1 deletion mice was reversed. These results demonstrate that T-bet 
      expression mediated by the mTOR pathway influences the CD4(+) T cell count in 
      mice with Candida sepsis.
CI  - Copyright (c) 2020 Bai, Wang, Han and Cui.
FAU - Bai, Guangxu
AU  - Bai G
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 
      China.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 
      China.
FAU - Han, Wen
AU  - Han W
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 
      China.
FAU - Cui, Na
AU  - Cui N
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 
      China.
AD  - Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking 
      Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
AD  - Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of 
      Invasive Fungal Diseases, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20200505
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC7214724
OTO - NOTNLM
OT  - CD4+ T cell count
OT  - Murine Sepsis Score
OT  - T-bet
OT  - lethal Candida sepsis
OT  - mammalian target of rapamycin
EDAT- 2020/05/21 06:00
MHDA- 2020/05/21 06:01
PMCR- 2020/05/05
CRDT- 2020/05/21 06:00
PHST- 2020/01/06 00:00 [received]
PHST- 2020/04/07 00:00 [accepted]
PHST- 2020/05/21 06:00 [entrez]
PHST- 2020/05/21 06:00 [pubmed]
PHST- 2020/05/21 06:01 [medline]
PHST- 2020/05/05 00:00 [pmc-release]
AID - 10.3389/fmicb.2020.00835 [doi]
PST - epublish
SO  - Front Microbiol. 2020 May 5;11:835. doi: 10.3389/fmicb.2020.00835. eCollection 
      2020.