Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains

Herpes simplex virus 1 (HSV-1) infects the majority of the human population and can induce encephalitis, which is the most common cause of sporadic, fatal encephalitis. An increase of microglia is detected in the brains of encephalitis patients. The issues regarding whether and how microglia protect...

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Autores principales:	Meng-Shan Tsai, Li-Chiu Wang, Hsien-Yang Tsai, Yu-Jheng Lin, Hua-Lin Wu, Shun-Fen Tzeng, Sheng-Min Hsu, Shun-Hua Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	herpes simplex virus 1 encephalitis brain T cells microglia interferon Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/ec182a84f82d4a55a3e1763305c001af
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spelling	oai:doaj.org-article:ec182a84f82d4a55a3e1763305c001af2021-11-25T17:56:51ZMicroglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains10.3390/ijms2222124571422-00671661-6596https://doaj.org/article/ec182a84f82d4a55a3e1763305c001af2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12457https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Herpes simplex virus 1 (HSV-1) infects the majority of the human population and can induce encephalitis, which is the most common cause of sporadic, fatal encephalitis. An increase of microglia is detected in the brains of encephalitis patients. The issues regarding whether and how microglia protect the host and neurons from HSV-1 infection remain elusive. Using a murine infection model, we showed that HSV-1 infection on corneas increased the number of microglia to outnumber those of infiltrating leukocytes (macrophages, neutrophils, and T cells) and enhanced microglia activation in brains. HSV-1 antigens were detected in brain neurons, which were surrounded by microglia. Microglia depletion increased HSV-1 lethality of mice with elevated brain levels of viral loads, infected neurons, neuron loss, CD4 T cells, CD8 T cells, neutrophils, interferon (IFN)-β, and IFN-γ. In vitro studies demonstrated that microglia from infected mice reduced virus infectivity. Moreover, microglia induced IFN-β and the signaling pathway of signal transducer and activator of transcription (STAT) 1 to inhibit viral replication and damage of neurons. Our study reveals how microglia protect the host and neurons from HSV-1 infection.Meng-Shan TsaiLi-Chiu WangHsien-Yang TsaiYu-Jheng LinHua-Lin WuShun-Fen TzengSheng-Min HsuShun-Hua ChenMDPI AGarticleherpes simplex virus 1encephalitisbrainT cellsmicrogliainterferonBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12457, p 12457 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	herpes simplex virus 1 encephalitis brain T cells microglia interferon Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	herpes simplex virus 1 encephalitis brain T cells microglia interferon Biology (General) QH301-705.5 Chemistry QD1-999 Meng-Shan Tsai Li-Chiu Wang Hsien-Yang Tsai Yu-Jheng Lin Hua-Lin Wu Shun-Fen Tzeng Sheng-Min Hsu Shun-Hua Chen Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains
description	Herpes simplex virus 1 (HSV-1) infects the majority of the human population and can induce encephalitis, which is the most common cause of sporadic, fatal encephalitis. An increase of microglia is detected in the brains of encephalitis patients. The issues regarding whether and how microglia protect the host and neurons from HSV-1 infection remain elusive. Using a murine infection model, we showed that HSV-1 infection on corneas increased the number of microglia to outnumber those of infiltrating leukocytes (macrophages, neutrophils, and T cells) and enhanced microglia activation in brains. HSV-1 antigens were detected in brain neurons, which were surrounded by microglia. Microglia depletion increased HSV-1 lethality of mice with elevated brain levels of viral loads, infected neurons, neuron loss, CD4 T cells, CD8 T cells, neutrophils, interferon (IFN)-β, and IFN-γ. In vitro studies demonstrated that microglia from infected mice reduced virus infectivity. Moreover, microglia induced IFN-β and the signaling pathway of signal transducer and activator of transcription (STAT) 1 to inhibit viral replication and damage of neurons. Our study reveals how microglia protect the host and neurons from HSV-1 infection.
format	article
author	Meng-Shan Tsai Li-Chiu Wang Hsien-Yang Tsai Yu-Jheng Lin Hua-Lin Wu Shun-Fen Tzeng Sheng-Min Hsu Shun-Hua Chen
author_facet	Meng-Shan Tsai Li-Chiu Wang Hsien-Yang Tsai Yu-Jheng Lin Hua-Lin Wu Shun-Fen Tzeng Sheng-Min Hsu Shun-Hua Chen
author_sort	Meng-Shan Tsai
title	Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains
title_short	Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains
title_full	Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains
title_fullStr	Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains
title_full_unstemmed	Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains
title_sort	microglia reduce herpes simplex virus 1 lethality of mice with decreased t cell and interferon responses in brains
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ec182a84f82d4a55a3e1763305c001af
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Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains

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