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Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics

Thousands of people die each year from Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV), probably due to exacerbation of the inflammatory response that impairs the course of the disease. Microglia are mononuclear phagocytic cells located within the parenchyma of the central...

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Autores principales: Zhao, Guanyu, Gao, Yan, Zhang, Jiaqi, Zhang, He, Xie, Changzhan, Nan, Fulong, Feng, Sheng, Ha, Zhuo, Li, Chenghui, Zhu, Xiangyu, Li, Zhuoxin, Zhang, Ping, Zhang, Ying, Lu, Huijun, Jin, Ningyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511957/
https://www.ncbi.nlm.nih.gov/pubmed/36171749
http://dx.doi.org/10.3389/fmicb.2022.989183
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author Zhao, Guanyu
Gao, Yan
Zhang, Jiaqi
Zhang, He
Xie, Changzhan
Nan, Fulong
Feng, Sheng
Ha, Zhuo
Li, Chenghui
Zhu, Xiangyu
Li, Zhuoxin
Zhang, Ping
Zhang, Ying
Lu, Huijun
Jin, Ningyi
author_facet Zhao, Guanyu
Gao, Yan
Zhang, Jiaqi
Zhang, He
Xie, Changzhan
Nan, Fulong
Feng, Sheng
Ha, Zhuo
Li, Chenghui
Zhu, Xiangyu
Li, Zhuoxin
Zhang, Ping
Zhang, Ying
Lu, Huijun
Jin, Ningyi
author_sort Zhao, Guanyu
collection PubMed
description Thousands of people die each year from Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV), probably due to exacerbation of the inflammatory response that impairs the course of the disease. Microglia are mononuclear phagocytic cells located within the parenchyma of the central nervous system; these play a key role in the innate immune response against JEV infections. However, the involvement of toll-like receptor 2 (TLR2) in the inflammatory response during the early stages of JEV infection in BV2 cells remains. Here, we evaluated protein profiles and determined the role of TLR2 in the inflammatory response of JEV-infected BV2 cells. High-depth tandem mass tags labeling for quantitative proteomics was used to assess JEV infected-BV2 cells and compare immune response profiles at 6, 12, and 24 h post-infection (hpi). In total, 212 upregulated proteins were detected at 6 hpi, 754 at 12 h, and 191 at 24 h. According to GO and KEGG enrichment analysis, the upregulated proteins showed enrichment for proteins related to the immune response. Parallel reaction monitoring tests, western blotting, and qPCR results showed that the adaptor protein MyD88 was not activated. The expression levels of key proteins downstream of MyD88, such as IRAK1, IRAK4, and TRAF6 did not increase; however, the expression levels of PI3K-AKT did increase. By inhibiting key proteins (TLR2, PI3K, and AKT) we confirmed that JEV activated TLR2, thus resulting in a robust inflammatory response. Consequently, the TLR2-PI3K-AKT signaling axis was proven to play a critical in the early stages of the JEV infection-induced inflammatory response in microglia.
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spelling pubmed-95119572022-09-27 Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics Zhao, Guanyu Gao, Yan Zhang, Jiaqi Zhang, He Xie, Changzhan Nan, Fulong Feng, Sheng Ha, Zhuo Li, Chenghui Zhu, Xiangyu Li, Zhuoxin Zhang, Ping Zhang, Ying Lu, Huijun Jin, Ningyi Front Microbiol Microbiology Thousands of people die each year from Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV), probably due to exacerbation of the inflammatory response that impairs the course of the disease. Microglia are mononuclear phagocytic cells located within the parenchyma of the central nervous system; these play a key role in the innate immune response against JEV infections. However, the involvement of toll-like receptor 2 (TLR2) in the inflammatory response during the early stages of JEV infection in BV2 cells remains. Here, we evaluated protein profiles and determined the role of TLR2 in the inflammatory response of JEV-infected BV2 cells. High-depth tandem mass tags labeling for quantitative proteomics was used to assess JEV infected-BV2 cells and compare immune response profiles at 6, 12, and 24 h post-infection (hpi). In total, 212 upregulated proteins were detected at 6 hpi, 754 at 12 h, and 191 at 24 h. According to GO and KEGG enrichment analysis, the upregulated proteins showed enrichment for proteins related to the immune response. Parallel reaction monitoring tests, western blotting, and qPCR results showed that the adaptor protein MyD88 was not activated. The expression levels of key proteins downstream of MyD88, such as IRAK1, IRAK4, and TRAF6 did not increase; however, the expression levels of PI3K-AKT did increase. By inhibiting key proteins (TLR2, PI3K, and AKT) we confirmed that JEV activated TLR2, thus resulting in a robust inflammatory response. Consequently, the TLR2-PI3K-AKT signaling axis was proven to play a critical in the early stages of the JEV infection-induced inflammatory response in microglia. Frontiers Media S.A. 2022-09-12 /pmc/articles/PMC9511957/ /pubmed/36171749 http://dx.doi.org/10.3389/fmicb.2022.989183 Text en Copyright © 2022 Zhao, Gao, Zhang, Zhang, Xie, Nan, Feng, Ha, Li, Zhu, Li, Zhang, Zhang, Lu and Jin. https://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 Microbiology
Zhao, Guanyu
Gao, Yan
Zhang, Jiaqi
Zhang, He
Xie, Changzhan
Nan, Fulong
Feng, Sheng
Ha, Zhuo
Li, Chenghui
Zhu, Xiangyu
Li, Zhuoxin
Zhang, Ping
Zhang, Ying
Lu, Huijun
Jin, Ningyi
Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics
title Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics
title_full Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics
title_fullStr Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics
title_full_unstemmed Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics
title_short Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics
title_sort toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in japanese encephalitis virus-infected mouse microglial cells by proteomics
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511957/
https://www.ncbi.nlm.nih.gov/pubmed/36171749
http://dx.doi.org/10.3389/fmicb.2022.989183
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