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<p>Arthropods are ancient vectors of infectious disease that alter the immune environment of the skin during feeding. The epidermis and its immune sentinels, including Langerhans cells, are critical for protection against ectoparasitic arthropods such as ticks. Here, we investigate how human Langerhans cells respond to clinical and experimental tick bites and concomitant infection with the tick-borne bacterium Borrelia burgdorferi. Using imaging, migration assays, immune spheroid models, and single-cell transcriptomic analysis of patient samples, we show that tick bites and tick saliva reprogram Langerhans cells to increase migration into lymphatic tissues, adopt a tolerogenic state marked by specific transcriptional programs, reduced ability to induce pro-inflammatory helper T cells, and enhanced promotion of type 2 and regulatory T cell responses. This shift dampens protective immunity and helps explain how ticks and their pathogens evade host defense and achieve efficient transmission.</p>

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Human epidermal Langerhans cells induce tolerance and hamper T cell function upon tick-borne pathogen transmission

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月28日

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  • Johanna Strobl,
  • Lisa Kleissl,
  • Julia Eder,
  • Sally Connolly,
  • Tobias Frey,
  • Laura Marie Gail,
  • Aglaja Kopf,
  • Sophie Weninger,
  • Mateusz Markowicz,
  • Pavlína Bartíková,
  • Christian Freystätter,
  • Klaus Schmetterer,
  • Herbert Strobl,
  • Hannes Stockinger,
  • Michiel Wijnveld,
  • Georg Stary

摘要

Arthropods are ancient vectors of infectious disease that alter the immune environment of the skin during feeding. The epidermis and its immune sentinels, including Langerhans cells, are critical for protection against ectoparasitic arthropods such as ticks. Here, we investigate how human Langerhans cells respond to clinical and experimental tick bites and concomitant infection with the tick-borne bacterium Borrelia burgdorferi. Using imaging, migration assays, immune spheroid models, and single-cell transcriptomic analysis of patient samples, we show that tick bites and tick saliva reprogram Langerhans cells to increase migration into lymphatic tissues, adopt a tolerogenic state marked by specific transcriptional programs, reduced ability to induce pro-inflammatory helper T cells, and enhanced promotion of type 2 and regulatory T cell responses. This shift dampens protective immunity and helps explain how ticks and their pathogens evade host defense and achieve efficient transmission.