ricinus species, and modeling data suggest a continuous further spread of this tick species to higher altitudes and latitudes ( 3).Įach year, thousands of patients affected by tick-borne diseases are admitted to hospitals around the world and there is still a significant gap in effective diagnosis, targeted treatment, or sufficient preventative measures. Since the summer of 2019, the European Centre for Disease Prevention and Control reported 7,563 novel locations in addition to previously known territorial distribution of I. Human hosts are affected primarily by diseases spread by the various species of the hard-tick family ( Ixodidae, genus Ixodes) distributed worldwide. Milder winters contribute to changes in wildlife-host populations, as well as shortening of the previously naturally occurring breaks in tick activity, resulting in a consistent increase in tick bite–associated (TB-associated) health complications annually ( 2). Steadily increasing tick prevalence has been reported globally in recent years, a trend that is predicted to increase with the rise in global temperatures and consequently more temperate climate ( 1). Ticks are hematophagous ectoparasites, with the skin representing the main interface of host-vector interaction that may become the site of tick-borne pathogen transmission. Collectively, we showed that tick feeding exerts profound changes on the skin immune network that interfere with the primary response against tick-borne pathogens. Preincubation of spirochetes with tick salivary gland extracts hampered accumulation of immune cells and increased spirochete loads. In early stages of Borrelia burgdorferi model infections, we detected strain-specific immune responses and close spatial relationships between macrophages and spirochetes. T cells upregulated tissue residency markers, while lymphocytic cytokine production was impaired. Following tick attachment, we observed rapidly occurring patterns of immunomodulation, including increases in neutrophils and cutaneous B and T cells. 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. However, the immunological consequences of tick feeding for human skin remain unclear. During cutaneous tick attachment, the feeding cavity becomes a site of transmission for tick salivary compounds and tick-borne pathogens.
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