Discovery of an Adaptive Neuroimmune Response Driving Itch and Fast Tick Removal with Implications for Preventing Pathogen Transmission

Doehl, J. S. P.; Serafim, T. D.; Doh, S.; Grugan, C. S.; Iniguez, E.; Rogerio, L.; Frigard, R.; Dey, R.; Cecilio, P.; Gu, X.; Tseng, P.-Y.; Da Silva Moreira, A.; Minai, M.; Oristian, J.; Ackerman, H.; Brooks, S.; Percopo, C.; Ng, S.-P.; Alves, D. A.; Tirloni, L.; Anderson, J. M.; Oliveira, F.; Kamhawi, S.; Sonenshine, D. E.; Marques, A.; Ribeiro, J. M. C.; Hoon, M.; Valenzuela, J. G.

doi:10.1101/2025.08.22.671835

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bioRxiv · 10.1101/2025.08.22.671835

Discovery of an Adaptive Neuroimmune Response Driving Itch and Fast Tick Removal with Implications for Preventing Pathogen Transmission

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Abstract

Acquired tick resistance (ATR) is well characterized in tick-exposed animals, compromising tick fitness through antibody-mediated activation of basophils. Yet, anti-tick vaccines inducing ATR have had limited success. Here, we describe a neuroimmune event preceding ATR that leads to rapid host-mediated tick removal. Tick-sensitized guinea pigs mechanically remove ticks within 3-6 hours via an acquired neuroimmune-induced itch response that correlates with increased dermal expression of itch-associated genes like OSM and skin infiltration by T cells and macrophages, independently of IgG and IgE antibodies. When we expose humans to ticks, a similar immune response is observed. Blocking T cells before tick sensitization prevents immune cell infiltration to bite sites and abrogates scratching and tick removal. This neuroimmune response is independent of Trpv1 as tick-sensitized guinea pigs treated with resiniferatoxin remove ticks effectively. Itch-induced tick removal or IITR offers a novel approach to tick-borne disease prevention through early tick detection and removal.

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Doehl, J. S. P., Serafim, T. D., Doh, S., Grugan, C. S., Iniguez, E., Rogerio, L., Frigard, R., Dey, R., Cecilio, P., Gu, X., Tseng, P.-Y., Da Silva Moreira, A., Minai, M., Oristian, J., Ackerman, H., Brooks, S., Percopo, C., Ng, S.-P., Alves, D. A., Tirloni, L., Anderson, J. M., Oliveira, F., Kamhawi, S., Sonenshine, D. E., Marques, A., Ribeiro, J. M. C., Hoon, M., Valenzuela, J. G.. 2025-08-28. Discovery of an Adaptive Neuroimmune Response Driving Itch and Fast Tick Removal with Implications for Preventing Pathogen Transmission. https://doi.org/10.1101/2025.08.22.671835

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