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

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-inf...

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Autores principales: Lin, Yu-Wen, Wang, Li-Chiu, Lee, Chien-Kuo, Chen, Shun-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093920/
https://www.ncbi.nlm.nih.gov/pubmed/30111869
http://dx.doi.org/10.1038/s41598-018-30631-2
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author Lin, Yu-Wen
Wang, Li-Chiu
Lee, Chien-Kuo
Chen, Shun-Hua
author_facet Lin, Yu-Wen
Wang, Li-Chiu
Lee, Chien-Kuo
Chen, Shun-Hua
author_sort Lin, Yu-Wen
collection PubMed
description 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.
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spelling pubmed-60939202018-08-20 Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses Lin, Yu-Wen Wang, Li-Chiu Lee, Chien-Kuo Chen, Shun-Hua Sci Rep Article 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. Nature Publishing Group UK 2018-08-15 /pmc/articles/PMC6093920/ /pubmed/30111869 http://dx.doi.org/10.1038/s41598-018-30631-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lin, Yu-Wen
Wang, Li-Chiu
Lee, Chien-Kuo
Chen, Shun-Hua
Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093920/
https://www.ncbi.nlm.nih.gov/pubmed/30111869
http://dx.doi.org/10.1038/s41598-018-30631-2
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