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Submitted on 30 Nov 2020
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The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection
Abdenour Abbas, Thien-Phong Vu Manh, Michael Valente, Nils Collinet, Noudjoud Attaf, Chuang Dong, Karima Naciri, Rabie Chelbi, Geoffray
Brelurut, Inaki Cervera-Marzal, et al.
To cite this version:
Abdenour Abbas, Thien-Phong Vu Manh, Michael Valente, Nils Collinet, Noudjoud Attaf, et al..
The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection. Nature
Immunology, Nature Publishing Group, 2020, 21 (9), pp.983-997. �10.1038/s41590-020-0731-4�. �hal-
The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection.
Abbas A, Vu Manh TP, Valente M, Collinet N, Attaf N, Dong C, Naciri K, Chelbi R, Brelurut G, Cervera‐
Marzal I, Rauwel B, Davignon JL, Bessou G, Thomas‐ Chollier M, Thieffry D, Villani AC, Milpied P, Dalod M, Tomasello E.
Nat Immunol. 2020 Sep;21(9):983‐997.
Epub 2020 Jul 20.
1 The activation trajectory of plasmacytoid dendritic cells in vivo during a 1
viral infection 2
Abdenour Abbas1,$, £ , Thien-Phong Vu Manh1,$, Michael Valente1, Nils 4
Collinet1, Noudjoud Attaf1, Chuang Dong1, Karima Naciri1, Rabie Chelbi1, 5
Geoffray Brelurut2, Inaki Cervera-Marzal1,§, Benjamin Rauwel3, Jean-Luc 6
Davignon3, Gilles Bessou1, Morgane Thomas-Chollier2, Denis Thieffry2, 7
Alexandra-Chloé Villani4,5, Pierre Milpied1, Marc Dalod1,*,#, Elena 8
1 Aix Marseille Univ, CNRS, INSERM, CIML, Centre d’Immunologie de 11
Marseille-Luminy, Turing Center for Living Systems, 13009 Marseille, France 12
2 Institut de Biologie de l’ENS (IBENS), Département de biologie, École normale 13
supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France 14
3 Centre de Physiopathologie Toulouse Purpan, INSERM UMR 1043, 31024 15
Toulouse, France 16
4 Broad Institute of MIT and Harvard, Cambridge, MA, USA 17
5 Center for Immunology and Inflammatory Diseases, Massachusetts General 18
Hospital, Boston, MA, USA 19
£ Current address: Institut Curie, PSL Research University, INSERM U932, Paris, 21
§ Current address: Eura Nova, Marseille, France.
$ Co-first author 25
# Co-senior author 26
** Corresponding author. Tel: +33 4 91 269407; E-mail: email@example.com 28
* Corresponding author. Tel: +33 4 91 269451; E-mail: firstname.lastname@example.org 29
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 36
more studies are needed to understand their orchestration. Here, we characterize in- 37
depth and link pDC activation states in animals infected by mouse cytomegalovirus, 38
by combining Ifnb1 reporter mice with flow cytometry, single-cell RNA sequencing, 39
confocal microscopy and a cognate CD4 T cell activation assay. We show that IFN-I 40
production and T cell activation were performed by the same pDC, but sequentially in 41
time and in different micro-anatomical locations. In addition, we show that pDC 42
commitment to IFN-I production was marked early on by their downregulation of LIFR 43
and promoted by cell-intrinsic TNF signaling. We propose a novel model of how 44
individual pDCs are endowed to exert different functions in vivo during a viral 45
infection in a manner tightly orchestrated in time and space.
Plasmacytoid dendritic cells (pDCs) produce massive amounts of type I 49
interferons (IFN-I) in response to virus-type stimuli1
, including in vivo during mouse 50
cytomegalovirus (MCMV) infection2, 3
. pDCs exert this function by engulfing material 51
derived from viruses or infected cells, and routing it to dedicated endosomes for toll- 52
like receptors 7/9 triggering and activation of the MyD88-to-IRF7 signaling pathway1
Soon after their discovery, pDCs were proposed to first produce IFN-I and 54
then acquire features of conventional dendritic cells (cDCs)4
, including dendrites and 55
the ability to present antigens4-7
, upon specific stimulation conditions. However, 56
adequate pDC purification methods and single-cell analysis tools were lacking to 57
prove this hypothesis. Indeed, when defined by few surface markers, pDCs can be 58
contaminated with cDC precursors8-10
, pDC-like cells11
, non-canonical CD8α+