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The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine

Enteroviruses infect gastrointestinal epithelium cells, cause multiple human diseases, and present public health risks worldwide. However, the mechanisms underlying host immune responses in intestinal mucosa against the early enterovirus infections remain elusive. Here, we showed that human enterovi...

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Autores principales: Su, Rui, Shereen, Muhammad Adnan, Zeng, Xiaofeng, Liang, Yicong, Li, Wen, Ruan, Zhihui, Li, Yongkui, Liu, Weiyong, Liu, Yingle, Wu, Kailang, Luo, Zhen, Wu, Jianguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683398/
https://www.ncbi.nlm.nih.gov/pubmed/33203755
http://dx.doi.org/10.1128/mBio.02540-20
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author Su, Rui
Shereen, Muhammad Adnan
Zeng, Xiaofeng
Liang, Yicong
Li, Wen
Ruan, Zhihui
Li, Yongkui
Liu, Weiyong
Liu, Yingle
Wu, Kailang
Luo, Zhen
Wu, Jianguo
author_facet Su, Rui
Shereen, Muhammad Adnan
Zeng, Xiaofeng
Liang, Yicong
Li, Wen
Ruan, Zhihui
Li, Yongkui
Liu, Weiyong
Liu, Yingle
Wu, Kailang
Luo, Zhen
Wu, Jianguo
author_sort Su, Rui
collection PubMed
description Enteroviruses infect gastrointestinal epithelium cells, cause multiple human diseases, and present public health risks worldwide. However, the mechanisms underlying host immune responses in intestinal mucosa against the early enterovirus infections remain elusive. Here, we showed that human enteroviruses including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1) predominantly induce type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), in cultured human normal and cancerous intestine epithelial cells (IECs), mouse intestine tissues, and human clinical intestine specimens. Mechanistic studies demonstrated that IFN-λ production is induced upon enterovirus infection through the Toll-like receptor 3/interferon regulatory factor 1 (TLR3/IRF1) signaling pathway in IECs. In turn, the supplementation of IFN-λ subsequently induces intrinsically antiviral responses against enterovirus replication. Notably, intraperitoneal injection in neonatal C57BL/6J mice with mouse recombinant IFN-λ2 protein represses EV71 replication and protects mice from viral lethal effects. Altogether, these results revealed a distinct mechanism by which the host elicited immune responses against enterovirus infections in intestine through activating the TLR3/IRF1/type III IFN axis. The new findings would provide an antiviral strategy for the prevention and treatment of enterovirus infections and associated diseases.
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spelling pubmed-76833982020-11-30 The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine Su, Rui Shereen, Muhammad Adnan Zeng, Xiaofeng Liang, Yicong Li, Wen Ruan, Zhihui Li, Yongkui Liu, Weiyong Liu, Yingle Wu, Kailang Luo, Zhen Wu, Jianguo mBio Research Article Enteroviruses infect gastrointestinal epithelium cells, cause multiple human diseases, and present public health risks worldwide. However, the mechanisms underlying host immune responses in intestinal mucosa against the early enterovirus infections remain elusive. Here, we showed that human enteroviruses including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1) predominantly induce type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), in cultured human normal and cancerous intestine epithelial cells (IECs), mouse intestine tissues, and human clinical intestine specimens. Mechanistic studies demonstrated that IFN-λ production is induced upon enterovirus infection through the Toll-like receptor 3/interferon regulatory factor 1 (TLR3/IRF1) signaling pathway in IECs. In turn, the supplementation of IFN-λ subsequently induces intrinsically antiviral responses against enterovirus replication. Notably, intraperitoneal injection in neonatal C57BL/6J mice with mouse recombinant IFN-λ2 protein represses EV71 replication and protects mice from viral lethal effects. Altogether, these results revealed a distinct mechanism by which the host elicited immune responses against enterovirus infections in intestine through activating the TLR3/IRF1/type III IFN axis. The new findings would provide an antiviral strategy for the prevention and treatment of enterovirus infections and associated diseases. American Society for Microbiology 2020-11-17 /pmc/articles/PMC7683398/ /pubmed/33203755 http://dx.doi.org/10.1128/mBio.02540-20 Text en Copyright © 2020 Su et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Su, Rui
Shereen, Muhammad Adnan
Zeng, Xiaofeng
Liang, Yicong
Li, Wen
Ruan, Zhihui
Li, Yongkui
Liu, Weiyong
Liu, Yingle
Wu, Kailang
Luo, Zhen
Wu, Jianguo
The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine
title The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine
title_full The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine
title_fullStr The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine
title_full_unstemmed The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine
title_short The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine
title_sort tlr3/irf1/type iii ifn axis facilitates antiviral responses against enterovirus infections in the intestine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683398/
https://www.ncbi.nlm.nih.gov/pubmed/33203755
http://dx.doi.org/10.1128/mBio.02540-20
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