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Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses
- Source :
- eLife, eLife, eLife Sciences Publication, 2018, 7, pp.e34273. ⟨10.7554/eLife.34273⟩, eLife, 2018, 7, pp.e34273. ⟨10.7554/eLife.34273⟩, eLife, Vol 7 (2018)
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
Abstract
- International audience; Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections.
- Subjects :
- Male
[SDV.IMM] Life Sciences [q-bio]/Immunology
QH301-705.5
Science
Interferon Regulatory Factor-7
viruses
Dengue
immunology
Interferon-gamma
Mice
Animals
Humans
dendritic cells
human
Biology (General)
mouse
Mice, Knockout
virus diseases
hemic and immune systems
Dengue Virus
Survival Analysis
virology
Killer Cells, Natural
Mice, Inbred C57BL
interferons
Disease Models, Animal
Gene Expression Regulation
inflammation
Host-Pathogen Interactions
Interferon Type I
Medicine
Chikungunya Fever
RNA, Viral
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Interferon Regulatory Factor-3
Chikungunya virus
Spleen
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Database :
- OpenAIRE
- Journal :
- eLife, eLife, eLife Sciences Publication, 2018, 7, pp.e34273. ⟨10.7554/eLife.34273⟩, eLife, 2018, 7, pp.e34273. ⟨10.7554/eLife.34273⟩, eLife, Vol 7 (2018)
- Accession number :
- edsair.pmid.dedup....ae1ccf9322a2ff451047425d1dae89b9