Tolerogenic programming renders dendritic cells more permissive to HCMV infection and limits their capacity to stimulate T cells. These findings suggest that tolerogenic DCs serve as a permissive cellular niche that may facilitate HCMV immune evasion.
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.