PMID- 36439161
OWN - NLM
STAT- MEDLINE
DCOM- 20221129
LR  - 20221129
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Indoleamine 2,3-dioxygenase 1 signaling orchestrates immune tolerance in 
      Echinococcus multilocularis-infected mice.
PG  - 1032280
LID - 10.3389/fimmu.2022.1032280 [doi]
LID - 1032280
AB  - The cestode Echinococcus multilocularis larva infection causes lethal zoonotic 
      alveolar echinococcosis (AE), a disease posing a great threat to the public 
      health worldwide. This persistent hepatic tumor-like disease in AE patients has 
      been largely attributed to aberrant T cell responses, of which Th1 responses are 
      impeded, whilst Th2 and regulatory T cell responses are elevated, creating an 
      immune tolerogenic microenvironment in the liver. However, the immune tolerance 
      mechanisms are not fully understood. Dendritic cells (DCs) are key cellular 
      components in facilitating immune tolerance in chronic diseases, including AE. 
      Here, we demonstrate that indoleamine 2,3-dioxygenase 1-deficient (IDO1(-/-)) 
      mice display less severe AE as compared to wild-type (WT) mice during the 
      infection. Mechanistically, IDO1 prevents optimal T cells responses by 
      programming DCs into a tolerogenic state. Specifically, IDO1 prevents the 
      maturation and migration potential of DCs, as shown by the significantly enhanced 
      expression of the antigen-presenting molecule (MHC II), costimulatory molecules 
      (CD80 and CD86), and chemokine receptors (CXCR4 and CCR7) in infected IDO1(-/-) 
      mice as compared to infected wild-type mice. More importantly, the tolerogenic 
      phenotype of DCs is partly reverted in IDO1(-/-) mice, as indicated by enhanced 
      activation, proliferation, and differentiation of both CD4(+) and CD8(+) - T 
      cells upon infection with Echinococcus multilocularis, in comparison with WT 
      mice. Interestingly, in absence of IDO1, CD4(+) T cells are prone to 
      differentiate to effector memory cells (CD44(+)CD62L(-)); in contrast, CD8(+) T 
      cells are highly biased to the central memory phenotype (CD44(+)CD62L(+)). 
      Overall, these data are the first to demonstrate the essential role of IDO1 
      signaling in inducing immunosuppression in mice infected with Echinococcus 
      multilocularis.
CI  - Copyright (c) 2022 Meng, Fu, Zhang, Mou, Liu and Fan.
FAU - Meng, Ru
AU  - Meng R
AD  - Research Center for High Altitude Medicine, Key Laboratory of High Altitude 
      Medicine (Ministry of Education), Key Laboratory of Application and Foundation 
      for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint 
      Research Key Lab for High Altitude Medicine), The Research Key Laboratory for 
      Echinococcosis of Qinghai Province, Qinghai University, Xining, China.
AD  - Academician Zhang Yong Innovation Center, Xining Animal Disease Control Center, 
      Xining, China.
FAU - Fu, Yong
AU  - Fu Y
AD  - Qinghai Academy of Animal Sciences and Veterinary Medicine, Qinghai University, 
      Xining, China.
FAU - Zhang, Yaogang
AU  - Zhang Y
AD  - Qinghai University Affiliated Hospital, Qinghai University, Xining, China.
FAU - Mou, Yalin
AU  - Mou Y
AD  - Qinghai University Affiliated Hospital, Qinghai University, Xining, China.
FAU - Liu, Gongguan
AU  - Liu G
AD  - Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of 
      Agriculture, MOE Joint International Research Laboratory of Animal Health and 
      Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 
      Nanjing, China.
FAU - Fan, Haining
AU  - Fan H
AD  - Research Center for High Altitude Medicine, Key Laboratory of High Altitude 
      Medicine (Ministry of Education), Key Laboratory of Application and Foundation 
      for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint 
      Research Key Lab for High Altitude Medicine), The Research Key Laboratory for 
      Echinococcosis of Qinghai Province, Qinghai University, Xining, China.
AD  - Qinghai University Affiliated Hospital, Qinghai University, Xining, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221111
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - Alveolar echinococcosis
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Echinococcus multilocularis
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Immune Tolerance
PMC - PMC9691980
OTO - NOTNLM
OT  - Echinococcus multilocularis
OT  - alveolar echinococcosis
OT  - dendritic cells
OT  - immunosuppression
OT  - indoleamine 2,3-dioxygenase 1
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- 2022/11/29 06:00
MHDA- 2022/11/30 06:00
PMCR- 2022/01/01
CRDT- 2022/11/28 04:32
PHST- 2022/08/30 00:00 [received]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/11/28 04:32 [entrez]
PHST- 2022/11/29 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.1032280 [doi]
PST - epublish
SO  - Front Immunol. 2022 Nov 11;13:1032280. doi: 10.3389/fimmu.2022.1032280. 
      eCollection 2022.