tetano
Editor, Senior Moderator
iScience
. 2025 Aug 18;28(9):113394.
doi: 10.1016/j.isci.2025.113394. eCollection 2025 Sep 19. Differential response of human plasmacytoid pre-dendritic cells to SARS-CoV-2 variants
Daria Kartasheva-Ebertz[SUP] 1 [/SUP], Dimitrios Topalis[SUP] 2 [/SUP], Claudia Umana-Diaz[SUP] 2 [/SUP], Okan Ayas[SUP] 1 [/SUP], Laurine Couture[SUP] 2 [/SUP], Pierre Tonnerre[SUP] 3 [/SUP], Jasna Medvedovic[SUP] 1 [/SUP], Laurent Meertens[SUP] 2 [/SUP], Vassili Soumelis[SUP] 1 4 [/SUP], Ali Amara[SUP] 2 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been involved in various waves of the COVID-19 pandemic and showed different pathogenicity and inflammatory potential. Whether they can induce different patterns of innate immune activation in antigen-presenting cells is poorly understood. Here, we investigated the ability of primary plasmacytoid pre-dendritic cells (pDC), type 2 dendritic cells (DC2), and monocytes isolated from healthy donors to respond to SARS-CoV-2 variants. Transcriptomic profiling using RNA sequencing revealed that pDC respond differentially to SARS-CoV-2 variants, unlike DC2 and monocytes. Functional studies showed that pDC undergo differential activation programs upon SARS-CoV-2 variant stimulation. The Alpha and Delta variants induced P1-/P2-pDC effector phenotypes, characterized by strong IFN-α production. In contrast, the Omicron variant predominantly triggered a T cell-activating P3 phenotype, with lower IFN-α and IFN-λ production, and stronger proinflammatory and CD4[SUP]+[/SUP]T cell responses. Our results indicate that SARS-CoV-2 variants can control pDC diversification pattern in different ways, which may influence disease severity.
Keywords: Immune response; Virology.
. 2025 Aug 18;28(9):113394.
doi: 10.1016/j.isci.2025.113394. eCollection 2025 Sep 19. Differential response of human plasmacytoid pre-dendritic cells to SARS-CoV-2 variants
Daria Kartasheva-Ebertz[SUP] 1 [/SUP], Dimitrios Topalis[SUP] 2 [/SUP], Claudia Umana-Diaz[SUP] 2 [/SUP], Okan Ayas[SUP] 1 [/SUP], Laurine Couture[SUP] 2 [/SUP], Pierre Tonnerre[SUP] 3 [/SUP], Jasna Medvedovic[SUP] 1 [/SUP], Laurent Meertens[SUP] 2 [/SUP], Vassili Soumelis[SUP] 1 4 [/SUP], Ali Amara[SUP] 2 [/SUP]
Affiliations
- PMID: 40970206
- PMCID: PMC12441710
- DOI: 10.1016/j.isci.2025.113394
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been involved in various waves of the COVID-19 pandemic and showed different pathogenicity and inflammatory potential. Whether they can induce different patterns of innate immune activation in antigen-presenting cells is poorly understood. Here, we investigated the ability of primary plasmacytoid pre-dendritic cells (pDC), type 2 dendritic cells (DC2), and monocytes isolated from healthy donors to respond to SARS-CoV-2 variants. Transcriptomic profiling using RNA sequencing revealed that pDC respond differentially to SARS-CoV-2 variants, unlike DC2 and monocytes. Functional studies showed that pDC undergo differential activation programs upon SARS-CoV-2 variant stimulation. The Alpha and Delta variants induced P1-/P2-pDC effector phenotypes, characterized by strong IFN-α production. In contrast, the Omicron variant predominantly triggered a T cell-activating P3 phenotype, with lower IFN-α and IFN-λ production, and stronger proinflammatory and CD4[SUP]+[/SUP]T cell responses. Our results indicate that SARS-CoV-2 variants can control pDC diversification pattern in different ways, which may influence disease severity.
Keywords: Immune response; Virology.