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Peer-reviewedCC BY 4.0European Journal of Immunology

Tolerogenic Programming Promotes Human Cytomegalovirus Permissiveness in Dendritic Cells

  • Katharina Rahmel‐Stein1
  • Jennifer Becker1
  • Berenike Lange1
  • Luise Krajewski1
  • Britta Eiz‐Vesper2,3
  • Ulrich Kalinke1,3
  1. 1Institute for Experimental Infection Research, TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School Hannover Germany
  2. 2Institute for Transfusion Medicine and Transplant Engineering Hannover Medical School Hannover Germany
  3. 3Cluster of Excellence ‐ Resolving Infection Susceptibility (RESIST, EXC 2155) Hannover Medical School Hannover Germany
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Abstract

Dendritic cells (DCs) are important targets of human cytomegalovirus (HCMV), yet the factors determining their permissiveness to infection remain incompletely understood. We previously identified a CD1a−/CD86− monocyte‐derived DC (moDC) subset with a tolerogenic transcriptional profile and increased susceptibility to HCMV. To test whether tolerogenic programming promotes DC permissiveness, we generated tolerogenic DCs (tolDCs) using vitamin D3 (VitD3), dexamethasone (Dexa), or their combination. TolDCs treated with Dexa alone or with VitD3+Dexa showed a maturation‐resistant phenotype, whereas VitD3‐treated cells retained partial responsiveness to maturation stimuli. Compared with conventional moDCs, tolDCs were more susceptible to HCMV infection. Functionally, HCMV‐exposed tolDCs induced markedly weaker CD4+ and CD8+ T‐cell proliferation, with Dexa‐treated cells showing the lowest stimulatory capacity. Together, these findings identify tolDCs as a permissive niche for HCMV and suggest that the virus may exploit regulatory DC states to evade immune control.

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Cite

BibTeXRIS
BibTeX
@article{rahmelstein2026tolerogenic,
  title = {{Tolerogenic Programming Promotes Human Cytomegalovirus Permissiveness in Dendritic Cells}},
  author = {Katharina Rahmel‐Stein and Jennifer Becker and Berenike Lange and Luise Krajewski and Britta Eiz‐Vesper and Ulrich Kalinke},
  journal = {European Journal of Immunology},
  year = {2026},
  month = oct,
  doi = {10.1002/eji.70306},
  url = {https://doi.org/10.1002/eji.70306},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Tolerogenic Programming Promotes Human Cytomegalovirus Permissiveness in Dendritic Cells
AU  - Katharina Rahmel‐Stein
AU  - Jennifer Becker
AU  - Berenike Lange
AU  - Luise Krajewski
AU  - Britta Eiz‐Vesper
AU  - Ulrich Kalinke
PY  - 2026
DA  - 2026/10/28
JO  - European Journal of Immunology
DO  - 10.1002/eji.70306
UR  - https://doi.org/10.1002/eji.70306
AB  - Dendritic cells (DCs) are important targets of human cytomegalovirus (HCMV), yet the factors determining their permissiveness to infection remain incompletely understood. We previously identified a CD1a−/CD86− monocyte‐derived DC (moDC) subset with a tolerogenic transcriptional profile and increased susceptibility to HCMV. To test whether tolerogenic programming promotes DC permissiveness, we generated tolerogenic DCs (tolDCs) using vitamin D3 (VitD3), dexamethasone (Dexa), or their combination. TolDCs treated with Dexa alone or with VitD3+Dexa showed a maturation‐resistant phenotype, whereas VitD3‐treated cells retained partial responsiveness to maturation stimuli. Compared with conventional moDCs, tolDCs were more susceptible to HCMV infection. Functionally, HCMV‐exposed tolDCs induced markedly weaker CD4+ and CD8+ T‐cell proliferation, with Dexa‐treated cells showing the lowest stimulatory capacity. Together, these findings identify tolDCs as a permissive niche for HCMV and suggest that the virus may exploit regulatory DC states to evade immune control.
SN  - 0014-2980
SN  - 1521-4141
ER  -