Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses

Abstract Enterovirus A71 (EV-A71) infection can induce encephalitis, which causes death or long-term neurological sequelae, especially in young children. Using a murine infection model, we searched for anti-EV-A71 agents, because effective therapies are not available to control fatal infection. In E...

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Autores principales:	Yu-Wen Lin, Li-Chiu Wang, Chien-Kuo Lee, Shun-Hua Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7142f68ce92d485c825b4e26108d7e61
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spelling	oai:doaj.org-article:7142f68ce92d485c825b4e26108d7e612021-12-02T15:08:15ZFlt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses10.1038/s41598-018-30631-22045-2322https://doaj.org/article/7142f68ce92d485c825b4e26108d7e612018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30631-2https://doaj.org/toc/2045-2322Abstract Enterovirus A71 (EV-A71) infection can induce encephalitis, which causes death or long-term neurological sequelae, especially in young children. Using a murine infection model, we searched for anti-EV-A71 agents, because effective therapies are not available to control fatal infection. In EV-A71-infected mice, treatment with the hematopoietic growth factor, Fms-like tyrosine-kinase 3 ligand (Flt3 ligand) before infection reduced the lethality and tissue viral loads. Flt3 ligand failed to enhance the production of type I interferons. Instead, Flt3 ligand boosted the numbers of dendritic cells and, particularly lymphocytes in infected organs with an expansion of spleen B cells, and resulted in an increased titer of virus-specific antibody with neutralizing activity in the serum. The protective effect of Flt3 ligand was abolished in B cell-deficient mice. Our findings revealed that Flt3 ligand administration promotes resistance to EV-A71 infection with enhanced B cell response in a mechanism rarely reported before.Yu-Wen LinLi-Chiu WangChien-Kuo LeeShun-Hua ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yu-Wen Lin Li-Chiu Wang Chien-Kuo Lee Shun-Hua Chen Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses
description	Abstract Enterovirus A71 (EV-A71) infection can induce encephalitis, which causes death or long-term neurological sequelae, especially in young children. Using a murine infection model, we searched for anti-EV-A71 agents, because effective therapies are not available to control fatal infection. In EV-A71-infected mice, treatment with the hematopoietic growth factor, Fms-like tyrosine-kinase 3 ligand (Flt3 ligand) before infection reduced the lethality and tissue viral loads. Flt3 ligand failed to enhance the production of type I interferons. Instead, Flt3 ligand boosted the numbers of dendritic cells and, particularly lymphocytes in infected organs with an expansion of spleen B cells, and resulted in an increased titer of virus-specific antibody with neutralizing activity in the serum. The protective effect of Flt3 ligand was abolished in B cell-deficient mice. Our findings revealed that Flt3 ligand administration promotes resistance to EV-A71 infection with enhanced B cell response in a mechanism rarely reported before.
format	article
author	Yu-Wen Lin Li-Chiu Wang Chien-Kuo Lee Shun-Hua Chen
author_facet	Yu-Wen Lin Li-Chiu Wang Chien-Kuo Lee Shun-Hua Chen
author_sort	Yu-Wen Lin
title	Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses
title_short	Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses
title_full	Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses
title_fullStr	Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses
title_full_unstemmed	Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses
title_sort	flt3 ligand treatment reduces enterovirus a71 lethality in mice with enhanced b cell responses
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7142f68ce92d485c825b4e26108d7e61
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Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses

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