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Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages

A systematic and flexible immunoregulatory network is required to ensure the proper outcome of antiviral immune signaling and maintain homeostasis during viral infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been extensively studied in infla...

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Autores principales: Zou, Ziqi, Li, Mengyao, Zhou, Yunlian, Li, Jiaying, Pan, Ting, Lai, Lihua, Wang, Qingqing, Zhang, Lining, Wang, Qun, Song, Yinjing, Zhang, Yuanyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017232/
https://www.ncbi.nlm.nih.gov/pubmed/33815396
http://dx.doi.org/10.3389/fimmu.2021.642715
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author Zou, Ziqi
Li, Mengyao
Zhou, Yunlian
Li, Jiaying
Pan, Ting
Lai, Lihua
Wang, Qingqing
Zhang, Lining
Wang, Qun
Song, Yinjing
Zhang, Yuanyuan
author_facet Zou, Ziqi
Li, Mengyao
Zhou, Yunlian
Li, Jiaying
Pan, Ting
Lai, Lihua
Wang, Qingqing
Zhang, Lining
Wang, Qun
Song, Yinjing
Zhang, Yuanyuan
author_sort Zou, Ziqi
collection PubMed
description A systematic and flexible immunoregulatory network is required to ensure the proper outcome of antiviral immune signaling and maintain homeostasis during viral infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been extensively studied in inflammatory response, apoptosis, and cancer. However, the function of TIPE2 in antiviral innate immunity is poorly clarified. In this study, we reported that the expression of TIPE2 declined at the early period and then climbed up in macrophages under RNA virus stimulation. Knockout of TIPE2 in the macrophages enhanced the antiviral capacity and facilitated type I interferon (IFN) signaling after RNA viral infection both in vitro and in vivo. Consistently, overexpression of TIPE2 inhibited the production of type I IFNs and pro-inflammatory cytokines, and thus promoted the viral infection. Moreover, TIPE2 restrained the activation of TBK1 and IRF3 in the retinoic acid inducible gene-I (RIG-I)-like receptors (RLR) signaling pathway by directly interacting with retinoic acid inducible gene-I (RIG-I). Taken together, our results suggested that TIPE2 suppresses the type I IFN response induced by RNA virus by targeting RIG-I and blocking the activation of downstream signaling. These findings will provide new insights to reveal the immunological function of TIPE2 and may help to develop new strategies for the clinical treatment of RNA viral infections.
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spelling pubmed-80172322021-04-03 Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages Zou, Ziqi Li, Mengyao Zhou, Yunlian Li, Jiaying Pan, Ting Lai, Lihua Wang, Qingqing Zhang, Lining Wang, Qun Song, Yinjing Zhang, Yuanyuan Front Immunol Immunology A systematic and flexible immunoregulatory network is required to ensure the proper outcome of antiviral immune signaling and maintain homeostasis during viral infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been extensively studied in inflammatory response, apoptosis, and cancer. However, the function of TIPE2 in antiviral innate immunity is poorly clarified. In this study, we reported that the expression of TIPE2 declined at the early period and then climbed up in macrophages under RNA virus stimulation. Knockout of TIPE2 in the macrophages enhanced the antiviral capacity and facilitated type I interferon (IFN) signaling after RNA viral infection both in vitro and in vivo. Consistently, overexpression of TIPE2 inhibited the production of type I IFNs and pro-inflammatory cytokines, and thus promoted the viral infection. Moreover, TIPE2 restrained the activation of TBK1 and IRF3 in the retinoic acid inducible gene-I (RIG-I)-like receptors (RLR) signaling pathway by directly interacting with retinoic acid inducible gene-I (RIG-I). Taken together, our results suggested that TIPE2 suppresses the type I IFN response induced by RNA virus by targeting RIG-I and blocking the activation of downstream signaling. These findings will provide new insights to reveal the immunological function of TIPE2 and may help to develop new strategies for the clinical treatment of RNA viral infections. Frontiers Media S.A. 2021-03-19 /pmc/articles/PMC8017232/ /pubmed/33815396 http://dx.doi.org/10.3389/fimmu.2021.642715 Text en Copyright © 2021 Zou, Li, Zhou, Li, Pan, Lai, Wang, Zhang, Wang, Song and Zhang. 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
Zou, Ziqi
Li, Mengyao
Zhou, Yunlian
Li, Jiaying
Pan, Ting
Lai, Lihua
Wang, Qingqing
Zhang, Lining
Wang, Qun
Song, Yinjing
Zhang, Yuanyuan
Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages
title Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages
title_full Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages
title_fullStr Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages
title_full_unstemmed Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages
title_short Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages
title_sort tumor necrosis factor-α-induced protein 8-like 2 negatively regulates innate immunity against rna virus by targeting rig-i in macrophages
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017232/
https://www.ncbi.nlm.nih.gov/pubmed/33815396
http://dx.doi.org/10.3389/fimmu.2021.642715
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