Transcriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses
Increasing cases related to the pathogenicity of Enterovirus D68 (EV-D68) have made it a growing worldwide public health concern, especially due to increased severe respiratory illness and acute flaccid myelitis (AFM) in children. There are currently no vaccines or medicines to prevent or treat EV-D...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:c4362cab16114c129772c2c66c7932692021-11-30T13:11:26ZTranscriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses1664-322410.3389/fimmu.2021.749618https://doaj.org/article/c4362cab16114c129772c2c66c7932692021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.749618/fullhttps://doaj.org/toc/1664-3224Increasing cases related to the pathogenicity of Enterovirus D68 (EV-D68) have made it a growing worldwide public health concern, especially due to increased severe respiratory illness and acute flaccid myelitis (AFM) in children. There are currently no vaccines or medicines to prevent or treat EV-D68 infections. Herein, we performed genome-wide transcriptional profiling of EV-D68-infected human rhabdomyosarcoma (RD) cells to investigate host-pathogen interplay. RNA sequencing and subsequent experiments revealed that EV-D68 infection induced a profound transcriptional dysregulation of host genes, causing significantly elevated inflammatory responses and altered antiviral immune responses. In particular, triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in highly activated TREM-1 signaling processes, acting as an important mediator in EV-D68 infection, and it is related to upregulation of interleukin 8 (IL-8), IL-6, IL-12p70, IL-1β, and tumor necrosis factor alpha (TNF-α). Further results demonstrated that NF-κB p65 was essential for EV-D68-induced TREM-1 upregulation. Moreover, inhibition of the TREM1 signaling pathway by the specific inhibitor LP17 dampened activation of the p38 mitogen-activated protein kinase (MAPK) signaling cascade, suggesting that TREM-1 mainly transmits activation signals to phosphorylate p38 MAPK. Interestingly, treatment with LP17 to inhibit TREM-1 inhibited viral replication and infection. These findings imply the pathogenic mechanisms of EV-D68 and provide critical insight into therapeutic intervention in enterovirus diseases.Jinyu LiJinyu LiShan YangSihua LiuYulu ChenHongyun LiuYazhi SuRuicun LiuYujun CuiYajun SongYue TengTao WangTao WangFrontiers Media S.A.articleEnterovirus D68transcriptomeTREM-1 signalingproinflammatory responseNF-κB signalingImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Enterovirus D68 transcriptome TREM-1 signaling proinflammatory response NF-κB signaling Immunologic diseases. Allergy RC581-607 |
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Enterovirus D68 transcriptome TREM-1 signaling proinflammatory response NF-κB signaling Immunologic diseases. Allergy RC581-607 Jinyu Li Jinyu Li Shan Yang Sihua Liu Yulu Chen Hongyun Liu Yazhi Su Ruicun Liu Yujun Cui Yajun Song Yue Teng Tao Wang Tao Wang Transcriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses |
| description |
Increasing cases related to the pathogenicity of Enterovirus D68 (EV-D68) have made it a growing worldwide public health concern, especially due to increased severe respiratory illness and acute flaccid myelitis (AFM) in children. There are currently no vaccines or medicines to prevent or treat EV-D68 infections. Herein, we performed genome-wide transcriptional profiling of EV-D68-infected human rhabdomyosarcoma (RD) cells to investigate host-pathogen interplay. RNA sequencing and subsequent experiments revealed that EV-D68 infection induced a profound transcriptional dysregulation of host genes, causing significantly elevated inflammatory responses and altered antiviral immune responses. In particular, triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in highly activated TREM-1 signaling processes, acting as an important mediator in EV-D68 infection, and it is related to upregulation of interleukin 8 (IL-8), IL-6, IL-12p70, IL-1β, and tumor necrosis factor alpha (TNF-α). Further results demonstrated that NF-κB p65 was essential for EV-D68-induced TREM-1 upregulation. Moreover, inhibition of the TREM1 signaling pathway by the specific inhibitor LP17 dampened activation of the p38 mitogen-activated protein kinase (MAPK) signaling cascade, suggesting that TREM-1 mainly transmits activation signals to phosphorylate p38 MAPK. Interestingly, treatment with LP17 to inhibit TREM-1 inhibited viral replication and infection. These findings imply the pathogenic mechanisms of EV-D68 and provide critical insight into therapeutic intervention in enterovirus diseases. |
| format |
article |
| author |
Jinyu Li Jinyu Li Shan Yang Sihua Liu Yulu Chen Hongyun Liu Yazhi Su Ruicun Liu Yujun Cui Yajun Song Yue Teng Tao Wang Tao Wang |
| author_facet |
Jinyu Li Jinyu Li Shan Yang Sihua Liu Yulu Chen Hongyun Liu Yazhi Su Ruicun Liu Yujun Cui Yajun Song Yue Teng Tao Wang Tao Wang |
| author_sort |
Jinyu Li |
| title |
Transcriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses |
| title_short |
Transcriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses |
| title_full |
Transcriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses |
| title_fullStr |
Transcriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses |
| title_full_unstemmed |
Transcriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses |
| title_sort |
transcriptomic profiling reveals a role for trem-1 activation in enterovirus d68 infection-induced proinflammatory responses |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/c4362cab16114c129772c2c66c793269 |
| work_keys_str_mv |
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