↓ Skip to main content

Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses

Overview of attention for article published in Journal of Neuroinflammation, April 2016
Altmetric Badge

About this Attention Score

  • Average Attention Score compared to outputs of the same age
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

twitter
2 X users

Citations

dimensions_citation
17 Dimensions

Readers on

mendeley
39 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses
Published in
Journal of Neuroinflammation, April 2016
DOI 10.1186/s12974-016-0551-5
Pubmed ID
Authors

Seong Bum Kim, Jin Young Choi, Erdenebileg Uyangaa, Ajit Mahadev Patil, Ferdaus Mohd Altaf Hossain, Jin Hur, Sang-Youel Park, John-Hwa Lee, Koanhoi Kim, Seong Kug Eo

Abstract

Japanese encephalitis (JE), a leading cause of viral encephalitis, is characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV). Indoleamine 2,3-dioxygenase (IDO) has been identified as an enzyme associated with immunoregulatory function. Although the regulatory role of IDO in viral replication has been postulated, the in vivo role of IDO activity has not been fully addressed in neurotropic virus-caused encephalitis. Mice in which IDO activity was inhibited by genetic ablation or using a specific inhibitor were examined for mortality and clinical signs after infection. Neuroinflammation was evaluated by central nervous system (CNS) infiltration of leukocytes and cytokine expression. IDO expression, viral burden, JEV-specific T-cell, and type I/II interferon (IFN-I/II) innate responses were also analyzed. Elevated expression of IDO activity in myeloid and neuron cells of the lymphoid and CNS tissues was closely associated with clinical signs of JE. Furthermore, inhibition of IDO activity enhanced resistance to JE, reduced the viral burden in lymphoid and CNS tissues, and resulted in early and increased CNS infiltration by Ly-6C(hi) monocytes, NK, CD4(+), and CD8(+) T-cells. JE amelioration in IDO-ablated mice was also associated with enhanced NK and JEV-specific T-cell responses. More interestingly, IDO ablation induced rapid enhancement of type I IFN (IFN-I) innate responses in CD11c(+) dendritic cells (DCs), including conventional and plasmacytoid DCs, following JEV infection. This enhanced IFN-I innate response in IDO-ablated CD11c(+) DCs was coupled with strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7, STAT1), and antiviral ISG genes (Mx1, Mx2, ISG49, ISG54, ISG56). IDO ablation also enhanced the IFN-I innate response in neuron cells, which may delay the spread of virus in the CNS. Finally, we identified that IDO ablation in myeloid cells derived from hematopoietic stem cells (HSCs) dominantly contributed to JE amelioration and that HSC-derived leukocytes played a key role in the enhanced IFN-I innate responses in the IDO-ablated environment. Inhibition of IDO activity ameliorated JE via enhancement of antiviral IFN-I/II innate and adaptive T-cell responses and increased CNS infiltration of peripheral leukocytes. Therefore, our data provide valuable insight into the use of IDO inhibition by specific inhibitors as a promising tool for therapeutic and prophylactic strategies against viral encephalitis caused by neurotropic viruses.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
Unknown 38 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 21%
Student > Bachelor 6 15%
Student > Ph. D. Student 6 15%
Student > Master 4 10%
Other 3 8%
Other 5 13%
Unknown 7 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 18%
Immunology and Microbiology 6 15%
Medicine and Dentistry 4 10%
Biochemistry, Genetics and Molecular Biology 3 8%
Arts and Humanities 2 5%
Other 8 21%
Unknown 9 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 April 2016.
All research outputs
#14,847,187
of 22,865,319 outputs
Outputs from Journal of Neuroinflammation
#1,662
of 2,643 outputs
Outputs of similar age
#170,036
of 299,111 outputs
Outputs of similar age from Journal of Neuroinflammation
#28
of 49 outputs
Altmetric has tracked 22,865,319 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,643 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 33rd percentile – i.e., 33% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 299,111 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 49 others from the same source and published within six weeks on either side of this one. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.