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IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses
- Source :
- Nature Communications. 13
- Publication Year :
- 2022
- Publisher :
- Springer Science and Business Media LLC, 2022.
-
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.
- Subjects :
- Multidisciplinary
Interleukin-6
SARS-CoV-2
Nogo Proteins
631/250/255/2514
article
COVID-19
Membrane Proteins
RNA-Binding Proteins
General Physics and Astronomy
631/250/262
13/106
General Chemistry
631/250/254
13
14
Toll-Like Receptor 2
General Biochemistry, Genetics and Molecular Biology
Mice
13/21
13/51
14/63
Animals
Cytokines
Humans
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....6894078c1439ff835f4fcc2c2ee842fc