新規の適応性神経免疫応答によるマダニ除去メカニズムの発見と病原体感染伝播予防への応用

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.