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Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers
Rabies virus (RABV) causes fatal encephalitis in mammals and poses a public health threat in many parts of the world. Vaccination remains the most effective means for prevention and control of rabies. Studies focusing on the mechanism of RABV immunogenicity are necessary for improvement of rabies va...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418000/ https://www.ncbi.nlm.nih.gov/pubmed/30906301 http://dx.doi.org/10.3389/fimmu.2019.00429 |
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author | Luo, Zhaochen Li, Yingying Zhou, Ming Lv, Lei Wu, Qiong Chen, Chen Zhang, Yachun Sui, Baokun Tu, Changchun Cui, Min Chen, Huanchun Fu, Zhen F. Zhao, Ling |
author_facet | Luo, Zhaochen Li, Yingying Zhou, Ming Lv, Lei Wu, Qiong Chen, Chen Zhang, Yachun Sui, Baokun Tu, Changchun Cui, Min Chen, Huanchun Fu, Zhen F. Zhao, Ling |
author_sort | Luo, Zhaochen |
collection | PubMed |
description | Rabies virus (RABV) causes fatal encephalitis in mammals and poses a public health threat in many parts of the world. Vaccination remains the most effective means for prevention and control of rabies. Studies focusing on the mechanism of RABV immunogenicity are necessary for improvement of rabies vaccines. Toll-like receptor 7 (TLR7), an innate receptor sensing single-stranded viral RNA, is important for the induction of innate and adaptive immunity. Our studies revealed that the absence of TLR7 led to a lower antibody production in mice immunized with RABV. It is further found that TLR7 deficiency affected the recruitment of germinal center (GC) B cells and led to lessened GCs formation. Consistently, there were less plasma cells (PCs) and antibody secreting cells (ASC) in TLR7(−/−) mice than those in wild type (WT) mice, resulting in impaired production of RABV-neutralizing antibodies (VNA). TLR7 deficiency also impaired the generation of memory B cells (MBCs) and the induction of secondary immune responses. Moreover, TLR7 deficiency down-regulated the induction of some cytokines/chemokines, especially IFN-γ, resulting in a Th2-biased antibody production. Overall, our results suggest that TLR7 facilitates the induction of the humoral immunity in response to RABV. |
format | Online Article Text |
id | pubmed-6418000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64180002019-03-22 Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers Luo, Zhaochen Li, Yingying Zhou, Ming Lv, Lei Wu, Qiong Chen, Chen Zhang, Yachun Sui, Baokun Tu, Changchun Cui, Min Chen, Huanchun Fu, Zhen F. Zhao, Ling Front Immunol Immunology Rabies virus (RABV) causes fatal encephalitis in mammals and poses a public health threat in many parts of the world. Vaccination remains the most effective means for prevention and control of rabies. Studies focusing on the mechanism of RABV immunogenicity are necessary for improvement of rabies vaccines. Toll-like receptor 7 (TLR7), an innate receptor sensing single-stranded viral RNA, is important for the induction of innate and adaptive immunity. Our studies revealed that the absence of TLR7 led to a lower antibody production in mice immunized with RABV. It is further found that TLR7 deficiency affected the recruitment of germinal center (GC) B cells and led to lessened GCs formation. Consistently, there were less plasma cells (PCs) and antibody secreting cells (ASC) in TLR7(−/−) mice than those in wild type (WT) mice, resulting in impaired production of RABV-neutralizing antibodies (VNA). TLR7 deficiency also impaired the generation of memory B cells (MBCs) and the induction of secondary immune responses. Moreover, TLR7 deficiency down-regulated the induction of some cytokines/chemokines, especially IFN-γ, resulting in a Th2-biased antibody production. Overall, our results suggest that TLR7 facilitates the induction of the humoral immunity in response to RABV. Frontiers Media S.A. 2019-03-08 /pmc/articles/PMC6418000/ /pubmed/30906301 http://dx.doi.org/10.3389/fimmu.2019.00429 Text en Copyright © 2019 Luo, Li, Zhou, Lv, Wu, Chen, Zhang, Sui, Tu, Cui, Chen, Fu and Zhao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Luo, Zhaochen Li, Yingying Zhou, Ming Lv, Lei Wu, Qiong Chen, Chen Zhang, Yachun Sui, Baokun Tu, Changchun Cui, Min Chen, Huanchun Fu, Zhen F. Zhao, Ling Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers |
title | Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers |
title_full | Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers |
title_fullStr | Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers |
title_full_unstemmed | Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers |
title_short | Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers |
title_sort | toll-like receptor 7 enhances rabies virus-induced humoral immunity by facilitating the formation of germinal centers |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418000/ https://www.ncbi.nlm.nih.gov/pubmed/30906301 http://dx.doi.org/10.3389/fimmu.2019.00429 |
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