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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.989183/full |
| _version_ | 1818056483838885888 |
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| author | Guanyu Zhao Yan Gao Jiaqi Zhang He Zhang He Zhang Changzhan Xie Fulong Nan Sheng Feng Zhuo Ha Zhuo Ha Chenghui Li Xiangyu Zhu Zhuoxin Li Ping Zhang Ying Zhang Huijun Lu Huijun Lu Ningyi Jin Ningyi Jin Ningyi Jin |
| author_facet | Guanyu Zhao Yan Gao Jiaqi Zhang He Zhang He Zhang Changzhan Xie Fulong Nan Sheng Feng Zhuo Ha Zhuo Ha Chenghui Li Xiangyu Zhu Zhuoxin Li Ping Zhang Ying Zhang Huijun Lu Huijun Lu Ningyi Jin Ningyi Jin Ningyi Jin |
| author_sort | Guanyu Zhao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T12:29:34Z |
| format | Article |
| id | doaj.art-3bd9625494684ac8859fd39c2e33600b |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-10T12:29:34Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-3bd9625494684ac8859fd39c2e33600b2022-12-22T01:48:51ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-09-011310.3389/fmicb.2022.989183989183Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomicsGuanyu Zhao0Yan Gao1Jiaqi Zhang2He Zhang3He Zhang4Changzhan Xie5Fulong Nan6Sheng Feng7Zhuo Ha8Zhuo Ha9Chenghui Li10Xiangyu Zhu11Zhuoxin Li12Ping Zhang13Ying Zhang14Huijun Lu15Huijun Lu16Ningyi Jin17Ningyi Jin18Ningyi Jin19College of Veterinary Medicine, College of Animal Science, Jilin University, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaResearch Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaResearch Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaCollege of Veterinary Medicine, College of Animal Science, Jilin University, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaResearch Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun, ChinaCollege of Veterinary Medicine, College of Animal Science, Jilin University, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaResearch Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun, ChinaThousands 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.https://www.frontiersin.org/articles/10.3389/fmicb.2022.989183/fullJapanese encephalitis virus (JEV)toll-like receptor 2 (TLR2)proteomicsinflammatory responsemicroglial |
| spellingShingle | Guanyu Zhao Yan Gao Jiaqi Zhang He Zhang He Zhang Changzhan Xie Fulong Nan Sheng Feng Zhuo Ha Zhuo Ha Chenghui Li Xiangyu Zhu Zhuoxin Li Ping Zhang Ying Zhang Huijun Lu Huijun Lu Ningyi Jin Ningyi Jin Ningyi Jin Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics Frontiers in Microbiology Japanese encephalitis virus (JEV) toll-like receptor 2 (TLR2) proteomics inflammatory response microglial |
| 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 | Japanese encephalitis virus (JEV) toll-like receptor 2 (TLR2) proteomics inflammatory response microglial |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.989183/full |
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