PMID- 34220803
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Japanese Encephalitis Virus Infected Human Monocyte-Derived Dendritic Cells 
      Activate a Transcriptional Network Leading to an Antiviral Inflammatory Response.
PG  - 638694
LID - 10.3389/fimmu.2021.638694 [doi]
LID - 638694
AB  - A comprehensive understanding of the human immune response to virus infection is 
      imperative for developing effective therapies, antivirals, and vaccines. 
      Dendritic cells (DCs) are among the first cells to encounter the virus and are 
      also key antigen-presenting cells that link the innate and adaptive immune 
      system. In this study, we focus on the human immune response to the 
      mosquito-borne Japanese encephalitis virus (JEV), which is the leading cause of 
      virus-induced encephalitis in south-east Asia and has the potential to become a 
      global pathogen. We describe the gene regulatory circuit of JEV infection in 
      human monocyte-derived DCs (moDCs) along with its functional validation. We 
      observe that JEV can productively infect human moDCs leading to robust 
      transcriptional activation of the interferon and NF-kappaB-mediated antiviral and 
      inflammatory pathways. This is accompanied with DC maturation and release of 
      pro-inflammatory cytokines and chemokines TNFalpha, IL-6, IL-8, IL-12, MCP-1. and 
      RANTES. JEV-infected moDCs activated T-regulatory cells (Tregs) in allogenic 
      mixed lymphocyte reactions (MLR) as seen by upregulated FOXP3 mRNA expression, 
      suggestive of a host response to reduce virus-induced immunopathology. The virus 
      also downregulated transcripts involved in Peroxisome Proliferator Activated 
      Receptor (PPAR) signalling and fatty acid metabolism pathways suggesting that 
      changes in cellular metabolism play a crucial role in driving the DC maturation 
      and antiviral responses. Collectively, our data describe and corroborate the 
      human DC transcriptional network that is engaged upon JEV sensing.
CI  - Copyright (c) 2021 Chauhan, Rathore, Sachan, Lacroix-Desmazes, Gupta, Awasthi, 
      Vrati and Kalia.
FAU - Chauhan, Shailendra
AU  - Chauhan S
AD  - Translational Health Science & Technology Institute, Faridabad, India.
FAU - Rathore, Deepak Kumar
AU  - Rathore DK
AD  - Translational Health Science & Technology Institute, Faridabad, India.
FAU - Sachan, Shilpa
AU  - Sachan S
AD  - Vaccine Immunology Laboratory, National Institute of Immunology, New Delhi, 
      India.
FAU - Lacroix-Desmazes, Sebastien
AU  - Lacroix-Desmazes S
AD  - Institut National de la Sante et de la Recherche Medicale, Centre de Recherche 
      des Cordeliers, Sorbonne Universite, Universite de Paris, Paris, France.
FAU - Gupta, Nimesh
AU  - Gupta N
AD  - Vaccine Immunology Laboratory, National Institute of Immunology, New Delhi, 
      India.
FAU - Awasthi, Amit
AU  - Awasthi A
AD  - Translational Health Science & Technology Institute, Faridabad, India.
FAU - Vrati, Sudhanshu
AU  - Vrati S
AD  - Translational Health Science & Technology Institute, Faridabad, India.
AD  - Regional Centre for Biotechnology, Faridabad, India.
FAU - Kalia, Manjula
AU  - Kalia M
AD  - Translational Health Science & Technology Institute, Faridabad, India.
AD  - Regional Centre for Biotechnology, Faridabad, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210617
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antiviral Agents)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antiviral Agents
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Encephalitis Virus, Japanese/*physiology
MH  - Encephalitis, Japanese/*immunology
MH  - Forkhead Transcription Factors/metabolism
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Immunity
MH  - Inflammation/*immunology
MH  - Inflammation Mediators
MH  - Interferon-gamma/genetics/metabolism
MH  - Lipid Metabolism
MH  - Monocytes/*immunology
MH  - NF-kappa B/genetics/metabolism
MH  - Peroxisome Proliferator-Activated Receptors/metabolism
MH  - T-Lymphocytes, Regulatory/*immunology
PMC - PMC8247639
OTO - NOTNLM
OT  - Japanese encephalitis virus
OT  - NF-kappaB
OT  - PPAR
OT  - Tregs
OT  - flavivirus
OT  - innate immune response
OT  - lipid metabolism
OT  - monocyte-derived dendritic cell
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- 2021/07/06 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/06/17
CRDT- 2021/07/05 10:00
PHST- 2020/12/07 00:00 [received]
PHST- 2021/05/04 00:00 [accepted]
PHST- 2021/07/05 10:00 [entrez]
PHST- 2021/07/06 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/06/17 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.638694 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jun 17;12:638694. doi: 10.3389/fimmu.2021.638694. eCollection 
      2021.