pDCs amplify tissue-resident memory CD8+ T cell responses during viral reinfection
Resident memory CD8+ T cells (Trms) are essential for protecting barrier nonlymphoid tissues (NLTs) against reinfection, yet the involvement of dendritic cells (DCs) in this process and the nature of Trm-DC interactions within these tissues remain poorly understood. Our study demonstrates that upon reactivation, memory CD8+ T cells located in the skin-independently of circulating memory counterparts-initiate the infiltration and maturation of plasmacytoid DCs (pDCs) in the tissue. This, in turn, promotes the maturation of conventional type 1 DCs (cDC1s) through type I IFN (IFN-I) signaling in a pDC-dependent manner. Depletion of pDCs or blocking IFN-I signaling disrupts this axis, severely impairing Trm-driven protection against secondary infections with vaccinia virus (VACV) in the skin. Notably, this pDC-dependent, IFN-I-mediated pathway is also essential for Trm-mediated protection against secondary respiratory infections with influenza A virus (IAV). Our findings uncover a crucial collaboration between Trm, pDCs, and cDC1s, offering new insights for enhancing vaccines.
Authors
- Elena Tomasello (ORCID: https://orcid.org/0000-0002-6839-5219)
- Elena Hernández‐García (ORCID: https://orcid.org/0000-0002-9018-5701)
- Marc Dalod (ORCID: https://orcid.org/0000-0002-6436-7966)
- Santos Mañes (ORCID: https://orcid.org/0000-0001-8023-957X)
- Sofía C. Khouili (ORCID: https://orcid.org/0000-0002-7333-789X)
- David Sancho (ORCID: https://orcid.org/0000-0003-2890-3984)
- Ana Redondo‐Urzainqui (ORCID: https://orcid.org/0000-0002-5551-4418)
- Sarai Martínez-Cano (ORCID: https://orcid.org/0000-0001-5883-3900)
- Elena Moya-Ruiz (ORCID: https://orcid.org/0000-0003-4157-5858)
- Francisco J. Cueto (ORCID: https://orcid.org/0000-0002-7457-9583)
- Salvador Iborra (ORCID: https://orcid.org/0000-0002-1607-1749)
- Miguel Á. Galán (ORCID: https://orcid.org/0000-0002-6695-1509)
- Manuel Rodrigo-Tapias (ORCID: https://orcid.org/0009-0009-6490-3114)
Institutions
- Universidad Complutense de Madrid (ES)
- Universidad de Alcalá (ES)
- Centro Nacional de Biotecnología (ES)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Centro de Investigaciones Biológicas Margarita Salas (ES)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2025-11-25
- DOI
- https://doi.org/10.1084/jem.20250099
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00