The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection.

Nature Immunology
Abdenour AbbasElena Tomasello

Abstract

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. In the present study, 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 these occurred 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 leukemia inhibitory factor receptor and was promoted by cell-intrinsic tumor necrosis factor signaling. We propose a new model for 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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Citations

Oct 28, 2020·Computational and Structural Biotechnology Journal·Geyang LuoBo Yan
Jan 5, 2021·Current Opinion in Rheumatology·Anthony ChangKichul Ko
Sep 24, 2020·Cell Reports·Rebecca LeylekJuliana Idoyaga
Jan 23, 2021·Annual Review of Immunology·Mar Cabeza-CabrerizoCaetano Reis E Sousa
Mar 13, 2021·Annual Review of Immunology·Xiangyun YinStephanie C Eisenbarth
May 1, 2021·International Journal of Molecular Sciences·Dóra BenczeKitti Pázmándi
Jul 27, 2021·Immunology·Heather M Giza, Leonia Bozzacco
Aug 9, 2021·Trends in Immunology·Laura C Van EyndhovenJurjen Tel
Sep 5, 2021·Nature Protocols·Marcela Alcántara-Hernández, Juliana Idoyaga
Oct 9, 2021·Clinical Science·Laura MarongiuFrancesca Granucci

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Methods Mentioned

BETA
confocal microscopy
flow cytometry
scRNA-seq
PCA
PCR
FACS

Software Mentioned

ImageJ
Gene Set Enrichment Analysis ( GSEA )
Monocle
Seurat R package
BubbleGUM
STAR
Gene
R
Seurat
GSEA

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