IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses.
Nat Commun
; 13(1): 5294, 2022 09 08.
Article
em En
| MEDLINE
| ID: mdl-36075894
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-6
/
Proteínas Nogo
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COVID-19
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article