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Tick feeding modulates the human skin immune landscape to facilitate tick-borne pathogen transmission
Johanna Strobl, … , Hannes Stockinger, Georg Stary
Johanna Strobl, … , Hannes Stockinger, Georg Stary
Published September 27, 2022
Citation Information: J Clin Invest. 2022;132(21):e161188. https://doi.org/10.1172/JCI161188.
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Research Article Immunology

Tick feeding modulates the human skin immune landscape to facilitate tick-borne pathogen transmission

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Abstract

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 and spirochetes. Preincubation of spirochetes with tick salivary gland extracts hampered accumulation of immune cells and increased spirochete loads. Collectively, we showed that tick feeding exerts profound changes on the skin immune network that interfere with the primary response against tick-borne pathogens.

Authors

Johanna Strobl, Verena Mündler, Sophie Müller, Anna Gindl, Sara Berent, Anna-Margarita Schötta, Lisa Kleissl, Clement Staud, Anna Redl, Luisa Unterluggauer, Ana E. Aguilar González, Sophie T. Weninger, Denise Atzmüller, Romana Klasinc, Gerold Stanek, Mateusz Markowicz, Hannes Stockinger, Georg Stary

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Figure 4

Skin sections of clinical and experimental tick bites harbor increased numbers of tissue-resident memory T cells.

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Skin sections of clinical and experimental tick bites harbor increased n...
(A–C) Lymphocytic infiltrate in TB (n = 11) and intraindividual HC samples (n = 11) as determined by immunolabeling of DAPI+ cells (A) and CD3 (B). Data shown as cell number per mm2 in dermis and epidermis. (C) Representative image of a CD3+ and DAPI-counterstained TB skin sample. Scale bar: 20 μm. (D and E) TRMs in TB (n = 11) and intraindividual HC samples (n = 11), CD69+ T cells (D), and CD103+ T cells (E). Data shown as cell number per mm2 in dermis and epidermis. (E) Right panel: Representative image of dermal and epidermal TRMs in TB skin. Scale bar: 100 μm. (F) Quantification of TCRγδ+ T cells in HC and TB skin (n = 4). Data shown as percentage of T cells (CD3+). (G) Representative image of DAPI, CD3, TCRαβ, and TCRγδ immunofluorescence staining (×20 magnification, left panels) in TB and HC skin and magnification (right panel). Arrows indicate TCRγδ+ T cells and asterisk shows TCRαβ positivity. Scale bar: 20 μm. In A–F, statistical analysis was performed using paired Student’s t test. **P < 0.01, ***P < 0.001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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