Local immune responses in tick-bite skin during SFTSV infection are associated with type I interferon signaling and monocyte-lineage cell recruitment

The skin harbors a complex immune microenvironment that integrates innate and adaptive components and plays a critical role in vector-borne pathogen transmission. To investigate immune responses during tick-mediated transmission of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), we analyzed skin from BALB/c mice bitten by artificially infected Amblyomma testudinarium nymphs. Skin samples were collected at time points corresponding to peak viral RNA levels (days 6-7 post-attachment) and analyzed by transcriptomics, followed by real-time PCR and immunohistochemical (IHC) analyses. Transcriptomic analysis revealed increased expression of immune-related genes, particularly those associated with type I interferon signaling. Interferon-stimulated genes (e.g., Rsad2, Ifit family members) and monocyte-associated markers (e.g., Ly6c2) were elevated in RNA sequencing data, while real-time PCR analysis showed similar trends but did not reach statistical significance. IHC revealed colocalization of viral antigens with macrophages in the infected skin, as characterized by Iba1 expression. Further analysis demonstrated a higher density of Ly6c2-positive inflammatory monocytes, consistent with transcriptomic observations. In addition, BST2 (Tetherin) expression was increased, consistent with activation of a localized Type I IFN-mediated antiviral response. However, the strong inflammatory response induced by tick feeding may obscure infection-specific transcriptional changes at these later time points. Overall, our findings demonstrate that tick-mediated SFTSV infection was associated with interferon-related gene expression and recruitment of monocyte-lineage cells at the skin interface, while highlighting the complex interplay between viral infection and tick-induced host responses.