PMID- 33679734
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20240226
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Uropathogenic Escherichia coli Infection Compromises the Blood-Testis Barrier by 
      Disturbing mTORC1-mTORC2 Balance.
PG  - 582858
LID - 10.3389/fimmu.2021.582858 [doi]
LID - 582858
AB  - The structural and functional destruction of the blood-testis barrier (BTB) 
      following uropathogenic E. coli (UPEC) infection may be a critical component of 
      the pathologic progress of orchitis. Recent findings indicate that the mammalian 
      target of the rapamycin (mTOR)-signaling pathway is implicated in the regulation 
      of BTB assembly and restructuring. To explore the mechanisms underlying BTB 
      damage induced by UPEC infection, we analyzed BTB integrity and the involvement 
      of the mTOR-signaling pathway using in vivo and in vitro UPEC-infection models. 
      We initially confirmed that soluble virulent factors secreted from UPEC trigger a 
      stress response in Sertoli cells and disturb adjacent cell junctions via 
      down-regulation of junctional proteins, including occludin, zonula occludens-1 
      (ZO-1), F-actin, connexin-43 (CX-43), beta-catenin, and N-cadherin. The BTB was 
      ultimately disrupted in UPEC-infected rat testes, and blood samples from 
      UPEC-induced orchitis in these animals were positive for anti-sperm antibodies. 
      Furthermore, we herein also demonstrated that mTOR complex 1 (mTORC1) 
      over-activation and mTORC2 suppression contributed to the disturbance in the 
      balance between BTB "opening" and "closing." More importantly, rapamycin (a 
      specific mTORC1 inhibitor) significantly restored the expression of cell-junction 
      proteins and exerted a protective effect on the BTB during UPEC infection. We 
      further confirmed that short-term treatment with rapamycin did not aggravate 
      spermatogenic degeneration in infected rats. Collectively, this study showed an 
      association between abnormal activation of the mTOR-signaling pathway and BTB 
      impairment during UPEC-induced orchitis, which may provide new insights into a 
      potential treatment strategy for testicular infection.
CI  - Copyright (c) 2021 Lu, Liu, Tursi, Yan, Cao, Che, Yang and Dong.
FAU - Lu, Yongning
AU  - Lu Y
AD  - Reproductive Medicine Centre, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Liu, Miao
AU  - Liu M
AD  - Reproductive Medicine Centre, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Tursi, Nicholas J
AU  - Tursi NJ
AD  - Department of Biology, University of Pennsylvania, Philadelphia, PA, United 
      States.
FAU - Yan, Bin
AU  - Yan B
AD  - Reproductive Medicine Centre, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Cao, Xiang
AU  - Cao X
AD  - Reproductive Medicine Centre, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Che, Qi
AU  - Che Q
AD  - Reproductive Medicine Centre, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Yang, Nianqin
AU  - Yang N
AD  - Reproductive Medicine Centre, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Dong, Xi
AU  - Dong X
AD  - Reproductive Medicine Centre, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210219
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Tight Junction Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
SB  - IM
MH  - Animals
MH  - Blood-Testis Barrier/*immunology/metabolism
MH  - Cells, Cultured
MH  - Escherichia coli Infections/*immunology/metabolism/microbiology
MH  - Humans
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/*immunology/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/*immunology/metabolism
MH  - Orchitis/immunology/metabolism/microbiology
MH  - Rats, Sprague-Dawley
MH  - Sertoli Cells/immunology/metabolism/microbiology
MH  - Spermatogenesis/immunology
MH  - Testis/immunology/metabolism
MH  - Tight Junction Proteins/immunology/metabolism
MH  - Urinary Tract Infections/*immunology/metabolism/microbiology
MH  - Uropathogenic Escherichia coli/*immunology/physiology
MH  - Rats
PMC - PMC7933507
OTO - NOTNLM
OT  - blood-testis barrier
OT  - male infertility
OT  - mammalian target of rapamycin
OT  - orchitis
OT  - uropathogenic E. coli
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/03/09 06:00
MHDA- 2021/06/29 06:00
PMCR- 2021/01/01
CRDT- 2021/03/08 05:50
PHST- 2020/07/13 00:00 [received]
PHST- 2021/01/19 00:00 [accepted]
PHST- 2021/03/08 05:50 [entrez]
PHST- 2021/03/09 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.582858 [doi]
PST - epublish
SO  - Front Immunol. 2021 Feb 19;12:582858. doi: 10.3389/fimmu.2021.582858. eCollection 
      2021.