biostudies-literatureStrobl JAustrian Science Fund FWFe161188https://www.ebi.ac.uk/biostudies/studies/S-EPMC9621130biostudies-literatureUnknown132(21)During cutaneous tick attachment, the feeding cavity becomes a site of transmission for tick salivary compounds and tick-borne pathogens. However, the immunological consequences of tick feeding for human skin remain unclear. Here, we assessed human skin and blood samples upon tick bite and developed a human skin explant model mimicking Ixodes ricinus bites and tick-borne pathogen infection. Following tick attachment, we observed rapidly occurring patterns of immunomodulation, including increases in neutrophils and cutaneous B and T cells. T cells upregulated tissue residency markers, while lymphocytic cytokine production was impaired. In early stages of Borrelia burgdorferi model infections, we detected strain-specific immune responses and close spatial relationships between macrophages anThe Journal of clinical investigationTick feeding modulates the human skin immune landscape to facilitate tick-borne pathogen transmission.PMC9621130P31494Berent SMundler VStanek GStockinger HMuller SUnterluggauer LKleissl LAguilar Gonzalez AEStary GGindl AStrobl JStaud CSchotta AMRedl AMarkowicz MWeninger STAtzmuller DKlasinc RfalseTick feeding modulates the human skin immune landscape to facilitate tick-borne pathogen transmission.During cutaneous tick attachment, the feeding cavity becomes a site of transmission for tick salivary compounds and tick-borne pathogens. However, the immunological consequences of tick feeding for human skin remain unclear. Here, we assessed human skin and blood samples upon tick bite and developed a human skin explant model mimicking Ixodes ricinus bites and tick-borne pathogen infection. Following tick attachment, we observed rapidly occurring patterns of immunomodulation, including increases in neutrophils and cutaneous B and T cells. T cells upregulated tissue residency markers, while lymphocytic cytokine production was impaired. In early stages of Borrelia burgdorferi model infections, we detected strain-specific immune responses and close spatial relationships between macrophages an2022-01-01T00:00:00Z2022 Nov2025-04-26T20:44:10.456Z2025-04-06T16:34:56.138ZS-EPMC96211303616629910.1172/JCI161188