Microglia retard dengue virus-induced acute viral encephalitis

Tsung Ting Tsai, Chia Ling Chen, Yee Shin Lin, Chih Peng Chang, Cheng Chieh Tsai, Yi Lin Cheng, Chao Ching Huang, Chien Jung Ho, Yi Chao Lee, Liang Tzung Lin, Ming Kai Jhan, Chiou Feng Lin

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis.

Original languageEnglish
Article number27670
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Jun 9

Fingerprint

Viral Encephalitis
Dengue Virus
Microglia
Virus Diseases
Cytotoxic T-Lymphocytes
Antiviral Agents
CD8-Positive T-Lymphocytes
Antigen-Presenting Cells
Lymphocyte Activation
Blood-Brain Barrier
Posture
Paralysis
Blood Vessels
Cell Differentiation
Hippocampus
Seizures
Cytokines
Inflammation
Mortality
Infection

All Science Journal Classification (ASJC) codes

  • General

Cite this

Tsai, Tsung Ting ; Chen, Chia Ling ; Lin, Yee Shin ; Chang, Chih Peng ; Tsai, Cheng Chieh ; Cheng, Yi Lin ; Huang, Chao Ching ; Ho, Chien Jung ; Lee, Yi Chao ; Lin, Liang Tzung ; Jhan, Ming Kai ; Lin, Chiou Feng. / Microglia retard dengue virus-induced acute viral encephalitis. In: Scientific reports. 2016 ; Vol. 6.
@article{33dc4d34d4cc41bfa59ba615f82e976b,
title = "Microglia retard dengue virus-induced acute viral encephalitis",
abstract = "Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis.",
author = "Tsai, {Tsung Ting} and Chen, {Chia Ling} and Lin, {Yee Shin} and Chang, {Chih Peng} and Tsai, {Cheng Chieh} and Cheng, {Yi Lin} and Huang, {Chao Ching} and Ho, {Chien Jung} and Lee, {Yi Chao} and Lin, {Liang Tzung} and Jhan, {Ming Kai} and Lin, {Chiou Feng}",
year = "2016",
month = "6",
day = "9",
doi = "10.1038/srep27670",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

Tsai, TT, Chen, CL, Lin, YS, Chang, CP, Tsai, CC, Cheng, YL, Huang, CC, Ho, CJ, Lee, YC, Lin, LT, Jhan, MK & Lin, CF 2016, 'Microglia retard dengue virus-induced acute viral encephalitis', Scientific reports, vol. 6, 27670. https://doi.org/10.1038/srep27670

Microglia retard dengue virus-induced acute viral encephalitis. / Tsai, Tsung Ting; Chen, Chia Ling; Lin, Yee Shin; Chang, Chih Peng; Tsai, Cheng Chieh; Cheng, Yi Lin; Huang, Chao Ching; Ho, Chien Jung; Lee, Yi Chao; Lin, Liang Tzung; Jhan, Ming Kai; Lin, Chiou Feng.

In: Scientific reports, Vol. 6, 27670, 09.06.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Microglia retard dengue virus-induced acute viral encephalitis

AU - Tsai, Tsung Ting

AU - Chen, Chia Ling

AU - Lin, Yee Shin

AU - Chang, Chih Peng

AU - Tsai, Cheng Chieh

AU - Cheng, Yi Lin

AU - Huang, Chao Ching

AU - Ho, Chien Jung

AU - Lee, Yi Chao

AU - Lin, Liang Tzung

AU - Jhan, Ming Kai

AU - Lin, Chiou Feng

PY - 2016/6/9

Y1 - 2016/6/9

N2 - Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis.

AB - Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis.

UR - http://www.scopus.com/inward/record.url?scp=84973855962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973855962&partnerID=8YFLogxK

U2 - 10.1038/srep27670

DO - 10.1038/srep27670

M3 - Article

C2 - 27279150

AN - SCOPUS:84973855962

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 27670

ER -