Microglia retard dengue virus-induced acute viral encephalitis.
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.
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University Taipei 110, Taiwan.
Tsung-Ting
TT
Tsai
Translational Research Center, Taipei Medical University, Taipei 110, Taiwan.
Chia-Ling
CL
Chen
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.|Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan.|Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Yee-Shin
YS
Lin
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.|Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan.|Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Chih-Peng
CP
Chang
Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan.
Cheng-Chieh
CC
Tsai
Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Yi-Lin
YL
Cheng
Department of Pediatric, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.|Department of Pediatric, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Chao-Ching
CC
Huang
Department of Pediatric, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Chien-Jung
CJ
Ho
The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Yi-Chao
YC
Lee
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University Taipei 110, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Liang-Tzung
LT
Lin
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University Taipei 110, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Ming-Kai
MK
Jhan
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University Taipei 110, Taiwan.|Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Chiou-Feng
CF
Lin
D000330:Aedes; D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003715:Dengue / Q000150:complications*; D003716:Dengue Virus / Q000472:pathogenicity / Q000502:physiology; D018792:Encephalitis, Viral / Q000209:etiology / Q000276:immunology*; D006624:Hippocampus / Q000166:cytology / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication
D016207:Cytokines