PMID- 31668132
OWN - NLM
STAT- MEDLINE
DCOM- 20200803
LR  - 20231019
IS  - 2150-5608 (Electronic)
IS  - 2150-5594 (Print)
IS  - 2150-5594 (Linking)
VI  - 10
IP  - 1
DP  - 2019 Dec
TI  - T-cell-specific mTOR deletion in mice ameliorated CD4(+) T-cell survival in 
      lethal sepsis induced by severe invasive candidiasis.
PG  - 892-901
LID - 10.1080/21505594.2019.1685151 [doi]
AB  - The mammalian target of rapamycin (mTOR) pathway can mediate T-cell survival; 
      however, the role of this pathway in T-cell survival during fungal sepsis is 
      unclear. Here, we investigated the role of the mTOR pathway in CD4(+) T-cell 
      survival in a mouse model of rapidly progressive lethal sepsis induced by severe 
      invasive candidiasis and explored the possible mechanism. The decrease in CD4(+) 
      T-cell survival following fungal sepsis was ameliorated in mice with a 
      T-cell-specific mTOR deletion, whereas it was exacerbated in mice with a 
      T-cell-specific tuberous sclerosis complex (TSC)1 deletion. To explore the 
      mechanism further, we measured expression of autophagy proteins light chain 3B 
      and p62/sequestosome 1 in CD4(+) T cells. Both proteins were increased in 
      T-cell-specific mTOR knockout mice but lower in T-cell-specific TSC1 knockout 
      mice. Transmission electron microscopy revealed that T-cell-specific mTOR 
      knockout mice had more autophagosomes than wild-type mice following fungal 
      sepsis. CD4(+) T-cell mTOR knockout decreased CD4(+) T-cell apoptosis in fungal 
      sepsis. Most notably, the T-cell-specific mTOR deletion mice had an increased 
      survival rate after fungal sepsis. These results suggest that the mTOR pathway 
      plays a vital role in CD4(+) T-cell survival during fungal sepsis, partly through 
      the autophagy-apoptosis pathway.
FAU - Wang, Hao
AU  - Wang H
AUID- ORCID: 0000-0001-7776-0882
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 
      China.
FAU - Bai, Guangxu
AU  - Bai G
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 
      China.
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 Science, Beijing, 
      China.
AD  - Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking 
      Union Medical College, Chinese Academy of Medical Science; Beijing Key Laboratory 
      for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, 
      Beijing, China.
FAU - Han, Wen
AU  - Han W
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 
      China.
FAU - Long, Yun
AU  - Long Y
AD  - Department of Critical Care Medicine, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Virulence
JT  - Virulence
JID - 101531386
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Systemic candidiasis
RN  - Tuberous Sclerosis 1
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Autophagy
MH  - CD4-Positive T-Lymphocytes/immunology/*pathology
MH  - Candidiasis/*immunology
MH  - Cell Survival/immunology
MH  - Gene Deletion
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Sepsis/*immunology/*microbiology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*genetics/*immunology
MH  - Tuberous Sclerosis/genetics
PMC - PMC6844314
OTO - NOTNLM
OT  - CD4+ T cells
OT  - Lethal fungal sepsis
OT  - autophagy
OT  - mammalian target of rapamycin
OT  - severe invasive candidiasis
EDAT- 2019/11/02 06:00
MHDA- 2020/08/04 06:00
PMCR- 2019/10/31
CRDT- 2019/11/01 06:00
PHST- 2019/11/01 06:00 [entrez]
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2020/08/04 06:00 [medline]
PHST- 2019/10/31 00:00 [pmc-release]
AID - 1685151 [pii]
AID - 10.1080/21505594.2019.1685151 [doi]
PST - ppublish
SO  - Virulence. 2019 Dec;10(1):892-901. doi: 10.1080/21505594.2019.1685151.