Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections
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.
Authors
- Thomas Baranek (ORCID: https://orcid.org/0000-0002-5651-0937)
- Elena Tomasello (ORCID: https://orcid.org/0000-0002-6839-5219)
- Sylvie Mathieu
- Nils Collinet
- Claude Grégoire (ORCID: https://orcid.org/0000-0003-3302-5274)
- Mauro Gaya (ORCID: https://orcid.org/0000-0002-7535-8678)
- Pierre Milpied (ORCID: https://orcid.org/0000-0003-1873-5358)
- Ana Zarubica (ORCID: https://orcid.org/0000-0001-5488-4137)
- Mathieu Fallet (ORCID: https://orcid.org/0000-0001-8144-6159)
- Khalissa Rahmani
- Frédéric Di Fiore (ORCID: https://orcid.org/0000-0001-7955-6594)
- Achille Broggi (ORCID: https://orcid.org/0000-0002-7244-2401)
- Sophie Mazzoli
- Marc Dalod (ORCID: https://orcid.org/0000-0002-6436-7966)
- Thien‐Phong Vu Manh (ORCID: https://orcid.org/0000-0002-0294-342X)
- Réjane Rua (ORCID: https://orcid.org/0000-0002-4289-3498)
- Manon Fabregue
- Michael Valente (ORCID: https://orcid.org/0000-0002-0844-9799)
- Sarah Sharkaoui
- Caroline Laprie (ORCID: https://orcid.org/0000-0003-2704-783X)
- Hien Tran (ORCID: https://orcid.org/0000-0002-2348-746X)
- Gilles Bessou
- Amandine Sansoni
- Lena Alexopoulou (ORCID: https://orcid.org/0000-0003-4619-697X)
- Lionel Chasson
- Marc Le Bert (ORCID: https://orcid.org/0000-0002-5945-3800)
- Narjess Haidar
- Camille Pierini-Malosse
- Capucine Guerry
- Bertrand Escalière
- Clemence Ngo
- Sarah Wurbel
Institutions
- Université de Tours (FR)
- Université d'Orléans (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Lund University (SE)
- Aix-Marseille Université (FR)
- OZ Biosciences (France) (FR)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Centre de Recherche en Cancérologie de Marseille (FR)
Publication Details
- Journal
- Nature Immunology
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1038/s41590-025-02288-3
- Citations
- 3
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Aix-Marseille Université
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Lunds Universitet
- Centre National de la Recherche Scientifique
- PHENOMIN