IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 09 2022
08 09 2022
Historique:
received:
23
08
2021
accepted:
08
08
2022
entrez:
8
9
2022
pubmed:
9
9
2022
medline:
14
9
2022
Statut:
epublish
Résumé
Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure to cytomegalovirus (CMV). IFITM3 also restricts IL-6 production in response to influenza and SARS-CoV-2. In dendritic cells, IFITM3 binds to the reticulon 4 isoform Nogo-B and promotes its proteasomal degradation. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and in the case of TLR2 responses, this process involves alteration of TLR2 cellular localization. Nogo-B deletion abrogates inflammatory cytokine responses and associated disease in virus-infected IFITM3-deficient mice. Thus, we uncover Nogo-B as a driver of viral pathogenesis and highlight an immunoregulatory pathway in which IFITM3 fine-tunes the responsiveness of myeloid cells to viral stimulation.
Identifiants
pubmed: 36075894
doi: 10.1038/s41467-022-32587-4
pii: 10.1038/s41467-022-32587-4
pmc: PMC9454482
doi:
Substances chimiques
Cytokines
0
IFITM3 protein, human
0
Interleukin-6
0
Membrane Proteins
0
Nogo Proteins
0
RNA-Binding Proteins
0
Toll-Like Receptor 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5294Subventions
Organisme : Wellcome Trust
ID : 207503/Z/17/Z
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : Medical Research Council
ID : MR/L018942/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S00971X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT098051
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V028448/1
Pays : United Kingdom
Organisme : HCRW_
ID : HCRW_HS-20-30
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108070/Z/15/Z
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R35 NS097283
Pays : United States
Informations de copyright
© 2022. The Author(s).
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