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

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 h via an acquired neuroimmune-induced itch response that correlates with increased dermal expression of itch-associated genes and skin infiltration by CD3+T cells and Iba-1+ macrophages, independent of IgG and IgE antibodies. Inhibiting the development of acquired T cell memory by averting naive lymphocyte egress from lymph nodes with the sphingosine-1-phosphate receptor modulator FTY720, before tick sensitization, prevents Iba-1+ macrophage and CD3+ T cell infiltration to the tick bite site and abrogates scratching and tick removal. This neuroimmune response is independent of Trpv1 as tick-sensitized guinea pigs treated with the Trpv1 agonist, resiniferatoxin, remove ticks effectively. Strikingly, prior exposure to a single tick is sufficient to generate a fast and active itch-induced tick removal (IITR) that is observed even in tick-attached sites distant from the location of previous tick exposure. IITR represents a novel approach to tick-borne disease prevention through early tick detection and fast removal.