Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction.
Antiviral immunity
TRAF2
TRAF3
Type I interferon
Journal
Cell & bioscience
ISSN: 2045-3701
Titre abrégé: Cell Biosci
Pays: England
ID NLM: 101561195
Informations de publication
Date de publication:
2019
2019
Historique:
received:
14
11
2018
accepted:
29
12
2018
entrez:
10
1
2019
pubmed:
10
1
2019
medline:
10
1
2019
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 30622699
doi: 10.1186/s13578-018-0268-5
pii: 268
pmc: PMC6318904
doi:
Types de publication
Journal Article
Langues
eng
Pagination
5Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI057555
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI064639
Pays : United States
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