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The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection
Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). What other functions pDCs exert in vivo during viral infections is controversial and more studies are needed to understand their orchestration. Here, we characterize in-depth and link pDC activation states in animal...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610367/ https://www.ncbi.nlm.nih.gov/pubmed/32690951 http://dx.doi.org/10.1038/s41590-020-0731-4 |
Sumario: | Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). What other functions pDCs exert in vivo during viral infections is controversial and more studies are needed to understand their orchestration. Here, we characterize in-depth and link pDC activation states in animals infected by mouse cytomegalovirus, by combining Ifnb1 reporter mice with flow cytometry, single-cell RNA sequencing, confocal microscopy and a cognate CD4 T cell activation assay. We show that IFN-I production and T cell activation were performed by the same pDC, but sequentially in time and in different micro-anatomical locations. In addition, we show that pDC commitment to IFN-I production was marked early on by their downregulation of LIFR and promoted by cell-intrinsic TNF signaling. We propose a novel model of how individual pDCs are endowed to exert different functions in vivo during a viral infection in a manner tightly orchestrated in time and space. |
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