Dysfunction of the plasmacytoid dendritic cells in enterovirus 71-induced HFMD affecting children.

The role of Plasmacytoid Dendritic Cells (pDCs) in Enterovirus-71 (EV71)-induced Hand, Foot, and Mouth Disease (HFMD) remains unclear. In this study, we investigated pDCs in severe HFMD patients infected with EV71. Flow cytometry revealed reduced pDC percentage in severe patients compared to healthy controls. In vitro, as EV71 replicated in pDCs, live cell numbers and levels of Interferon-alpha (IFN-a) and Interleukin (IL)-6 decreased, while IL-10 and Tumour Necrosis Factor-alpha (TNF-a) increased, particularly in critically ill patients. Notably, pDCs derived from critically ill patients exhibited significantly lower amplification rate and antiviral cytokine secretion compared to healthy controls. Analysis of the infection time course demonstrated that TLR7 expression rapidly increased at 6 h post-infection (h.p.i.), while its downstream signaling molecules reached higher levels by 24 h. TLR7 expression itself significantly decreased at 24 h.p.i. Pretreatment with the TLR7 inhibitor chloroquine (CQ) effectively suppressed the upregulation of TLR7. Concurrently, EV71 VP1 protein expression in the CQ-treated group remained at a moderate level throughout the time course, whereas it increased progressively in the untreated group. These findings suggest that EV71 may dynamically modulate the TLR7 pathway to evade innate immune recognition. In conclusion, EV71 may manipulate pDCs proliferation and cytokine secretion, evading the antiviral immune response, inducing cell tolerance, and promoting apoptosis. We speculate that EV71-induced inactivation of pDCs may contribute to disease deterioration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12865-026-00807-x.