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 - Jun 9 2016

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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

ASJC Scopus subject areas

  • General

Cite this

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

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.
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