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

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33 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

All Science Journal Classification (ASJC) codes

  • General

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