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Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction
BACKGROUND: TRAF3 is known as a central mediator of type I interferon (IFN) induction by various pattern recognition receptors, but the in vivo function of TRAF3 in host defense against viral infection is poorly defined due to the lack of a viable mouse model. RESULTS: Here we show that mice carryin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318904/ https://www.ncbi.nlm.nih.gov/pubmed/30622699 http://dx.doi.org/10.1186/s13578-018-0268-5 |
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author | Xie, Xiaoping Jin, Jin Zhu, Lele Jie, Zuliang Li, Yanchuan Zhao, Baoyu Cheng, Xuhong Li, Pingwei Sun, Shao-Cong |
author_facet | Xie, Xiaoping Jin, Jin Zhu, Lele Jie, Zuliang Li, Yanchuan Zhao, Baoyu Cheng, Xuhong Li, Pingwei Sun, Shao-Cong |
author_sort | Xie, Xiaoping |
collection | PubMed |
description | BACKGROUND: TRAF3 is known as a central mediator of type I interferon (IFN) induction by various pattern recognition receptors, but the in vivo function of TRAF3 in host defense against viral infection is poorly defined due to the lack of a viable mouse model. RESULTS: Here we show that mice carrying conditional deletion of TRAF3 in myeloid cells or dendritic cells do not have a significant defect in host defense against vesicular stomatitis virus (VSV) infection. However, whole-body inducible deletion of TRAF3 renders mice more sensitive to VSV infection. Consistently, TRAF3 was essential for type I IFN induction in mouse embryonic fibroblasts (MEFs) but not in macrophages. In dendritic cells, TRAF3 was required for type I IFN induction by TLR ligands but not by viruses. We further show that the IFN-regulating function is not unique to TRAF3, since TRAF2 is an essential mediator of type I IFN induction in several cell types, including macrophages, DCs, and MEFs. CONCLUSIONS: These findings suggest that both TRAF2 and TRAF3 play a crucial role in type I IFN induction, but their functions are cell type- and stimulus-specific. |
format | Online Article Text |
id | pubmed-6318904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63189042019-01-08 Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction Xie, Xiaoping Jin, Jin Zhu, Lele Jie, Zuliang Li, Yanchuan Zhao, Baoyu Cheng, Xuhong Li, Pingwei Sun, Shao-Cong Cell Biosci Research BACKGROUND: TRAF3 is known as a central mediator of type I interferon (IFN) induction by various pattern recognition receptors, but the in vivo function of TRAF3 in host defense against viral infection is poorly defined due to the lack of a viable mouse model. RESULTS: Here we show that mice carrying conditional deletion of TRAF3 in myeloid cells or dendritic cells do not have a significant defect in host defense against vesicular stomatitis virus (VSV) infection. However, whole-body inducible deletion of TRAF3 renders mice more sensitive to VSV infection. Consistently, TRAF3 was essential for type I IFN induction in mouse embryonic fibroblasts (MEFs) but not in macrophages. In dendritic cells, TRAF3 was required for type I IFN induction by TLR ligands but not by viruses. We further show that the IFN-regulating function is not unique to TRAF3, since TRAF2 is an essential mediator of type I IFN induction in several cell types, including macrophages, DCs, and MEFs. CONCLUSIONS: These findings suggest that both TRAF2 and TRAF3 play a crucial role in type I IFN induction, but their functions are cell type- and stimulus-specific. BioMed Central 2019-01-03 /pmc/articles/PMC6318904/ /pubmed/30622699 http://dx.doi.org/10.1186/s13578-018-0268-5 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Xie, Xiaoping Jin, Jin Zhu, Lele Jie, Zuliang Li, Yanchuan Zhao, Baoyu Cheng, Xuhong Li, Pingwei Sun, Shao-Cong Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction |
title | Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction |
title_full | Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction |
title_fullStr | Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction |
title_full_unstemmed | Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction |
title_short | Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction |
title_sort | cell type-specific function of traf2 and traf3 in regulating type i ifn induction |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318904/ https://www.ncbi.nlm.nih.gov/pubmed/30622699 http://dx.doi.org/10.1186/s13578-018-0268-5 |
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