Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus

Infection with flaviviruses causes mild to severe diseases, including viral hemorrhagic fever, vascular shock syndrome, and viral encephalitis. Several animal models explore the pathogenesis of viral encephalitis, as shown by neuron destruction due to neurotoxicity after viral infection. While neuro...

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Autores principales: Ming-Kai Jhan, Chia-Ling Chen, Ting-Jing Shen, Po-Chun Tseng, Yung-Ting Wang, Rahmat Dani Satria, Chia-Yi Yu, Chiou-Feng Lin
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:56797f7370064a3bab0a2363f9601c092021-11-25T17:12:28ZPolarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus10.3390/cells101131812073-4409https://doaj.org/article/56797f7370064a3bab0a2363f9601c092021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3181https://doaj.org/toc/2073-4409Infection with flaviviruses causes mild to severe diseases, including viral hemorrhagic fever, vascular shock syndrome, and viral encephalitis. Several animal models explore the pathogenesis of viral encephalitis, as shown by neuron destruction due to neurotoxicity after viral infection. While neuronal cells are injuries caused by inflammatory cytokine production following microglial/macrophage activation, the blockade of inflammatory cytokines can reduce neurotoxicity to improve the survival rate. This study investigated the involvement of macrophage phenotypes in facilitating CNS inflammation and neurotoxicity during flavivirus infection, including the Japanese encephalitis virus, dengue virus (DENV), and Zika virus. Mice infected with different flaviviruses presented encephalitis-like symptoms, including limbic seizure and paralysis. Histology indicated that brain lesions were identified in the hippocampus and surrounded by mononuclear cells. In those regions, both the infiltrated macrophages and resident microglia were significantly increased. RNA-seq analysis showed the gene profile shifting toward type 1 macrophage (M1) polarization, while M1 markers validated this phenomenon. Pharmacologically blocking C-C chemokine receptor 2 and tumor necrosis factor-α partly retarded DENV-induced M1 polarization. In summary, flavivirus infection, such as JEV and DENV, promoted type 1 macrophage polarization in the brain associated with encephalitic severity.Ming-Kai JhanChia-Ling ChenTing-Jing ShenPo-Chun TsengYung-Ting WangRahmat Dani SatriaChia-Yi YuChiou-Feng LinMDPI AGarticleflavivirusdengue virusencephalitismacrophagepolarizationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3181, p 3181 (2021)
institution DOAJ
collection DOAJ
language EN
topic flavivirus
dengue virus
encephalitis
macrophage
polarization
Biology (General)
QH301-705.5
spellingShingle flavivirus
dengue virus
encephalitis
macrophage
polarization
Biology (General)
QH301-705.5
Ming-Kai Jhan
Chia-Ling Chen
Ting-Jing Shen
Po-Chun Tseng
Yung-Ting Wang
Rahmat Dani Satria
Chia-Yi Yu
Chiou-Feng Lin
Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus
description Infection with flaviviruses causes mild to severe diseases, including viral hemorrhagic fever, vascular shock syndrome, and viral encephalitis. Several animal models explore the pathogenesis of viral encephalitis, as shown by neuron destruction due to neurotoxicity after viral infection. While neuronal cells are injuries caused by inflammatory cytokine production following microglial/macrophage activation, the blockade of inflammatory cytokines can reduce neurotoxicity to improve the survival rate. This study investigated the involvement of macrophage phenotypes in facilitating CNS inflammation and neurotoxicity during flavivirus infection, including the Japanese encephalitis virus, dengue virus (DENV), and Zika virus. Mice infected with different flaviviruses presented encephalitis-like symptoms, including limbic seizure and paralysis. Histology indicated that brain lesions were identified in the hippocampus and surrounded by mononuclear cells. In those regions, both the infiltrated macrophages and resident microglia were significantly increased. RNA-seq analysis showed the gene profile shifting toward type 1 macrophage (M1) polarization, while M1 markers validated this phenomenon. Pharmacologically blocking C-C chemokine receptor 2 and tumor necrosis factor-α partly retarded DENV-induced M1 polarization. In summary, flavivirus infection, such as JEV and DENV, promoted type 1 macrophage polarization in the brain associated with encephalitic severity.
format article
author Ming-Kai Jhan
Chia-Ling Chen
Ting-Jing Shen
Po-Chun Tseng
Yung-Ting Wang
Rahmat Dani Satria
Chia-Yi Yu
Chiou-Feng Lin
author_facet Ming-Kai Jhan
Chia-Ling Chen
Ting-Jing Shen
Po-Chun Tseng
Yung-Ting Wang
Rahmat Dani Satria
Chia-Yi Yu
Chiou-Feng Lin
author_sort Ming-Kai Jhan
title Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus
title_short Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus
title_full Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus
title_fullStr Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus
title_full_unstemmed Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus
title_sort polarization of type 1 macrophages is associated with the severity of viral encephalitis caused by japanese encephalitis virus and dengue virus
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/56797f7370064a3bab0a2363f9601c09
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