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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 Article has an altmetric score of 268

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 3

Intracellular cytokine staining reveals impaired T cell and ILC responses in skin and blood after tick bite.

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Intracellular cytokine staining reveals impaired T cell and ILC response...
(A) Ratio of CD4+/CD8+ T cells among T cells isolated from blood of TB (n = 16) and HC (n = 5). (B and C) Frequencies of cells expressing IL-4, IL-17a, and IFN-γ among T cells (B) and ILCs (C) in blood from TB (n = 16) and HC (n = 5) upon stimulation with PMA and ionomycin. (D) Ratio of CD4+/CD8+ T cells among skin T cells isolated from the site of TB and autologous HC skin (n = 16). (E and F) Frequencies of cells expressing IL-4, IL-17a, and IFN-γ among T cells (E) and ILCs (F) in TB skin and autologous HC (n = 16) upon stimulation with PMA and ionomycin. One symbol represents one patient, and dotted lines connect intraindividual samples. Data are presented as mean ± SEM. Statistical analysis was performed with unpaired (A–C) or paired (D–F) Student’s t test. *P < 0.05, **P < 0.01, ***P < 0.001.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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