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Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections

Ngo, Clemence ; Pierini-Malosse, Camille ; Rahmani, Khalissa ; Valente, Michael ; Collinet, Nils ; Bessou, Gilles ; Guerry, Capucine ; Fabregue, Manon ; Mathieu, Solene and Sharkaoui, Sarah , et al. (2025) In Nature Immunology 26(11). p.1962-1976
Abstract

Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process; however, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDCs or disrupt their interferon production often affect other cells, confounding interpretation. Here, to overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely coexpressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse cytomegalovirus and showed... (More)

Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process; however, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDCs or disrupt their interferon production often affect other cells, confounding interpretation. Here, to overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely coexpressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV-2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Immunology
volume
26
issue
11
pages
15 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:105017403647
  • pmid:41023479
ISSN
1529-2908
DOI
10.1038/s41590-025-02288-3
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
e8f8c6da-d331-48fc-abe4-f25cd8c8f662
date added to LUP
2025-12-08 11:39:11
date last changed
2025-12-09 03:00:14
@article{e8f8c6da-d331-48fc-abe4-f25cd8c8f662,
  abstract     = {{<p>Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process; however, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDCs or disrupt their interferon production often affect other cells, confounding interpretation. Here, to overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely coexpressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV-2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.</p>}},
  author       = {{Ngo, Clemence and Pierini-Malosse, Camille and Rahmani, Khalissa and Valente, Michael and Collinet, Nils and Bessou, Gilles and Guerry, Capucine and Fabregue, Manon and Mathieu, Solene and Sharkaoui, Sarah and Mazzoli, Sophie and Sansoni, Amandine and Fiore, Frederic and Laprie, Caroline and Alexopoulou, Lena and Gaya, Mauro and Gregoire, Claude and Broggi, Achille and Wurbel, Sarah and Rua, Réjane and Haidar, Narjess and Milpied, Pierre and Escalière, Bertrand and Vu Manh, Thien Phong and Fallet, Mathieu and Chasson, Lionel and Tran, Hien and Baranek, Thomas and Le Bert, Marc and Malissen, Bernard and Zarubica, Ana and Dalod, Marc and Tomasello, Elena}},
  issn         = {{1529-2908}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1962--1976}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Immunology}},
  title        = {{Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections}},
  url          = {{http://dx.doi.org/10.1038/s41590-025-02288-3}},
  doi          = {{10.1038/s41590-025-02288-3}},
  volume       = {{26}},
  year         = {{2025}},
}