Doehl Johannes S P, Serafim Tiago D, Doh Serena, Grugan Charles S, Iniguez Eva, Rogerio Luana, Frigard Ronja, Dey Ranadhir, Cecilio Pedro, Gu Xinglong, Tseng Pang-Yen, Moreira Aline Da Silva, Minai Mahnaz, Oristian James, Ackerman Hans, Brooks Steve, Percopo Caroline, Ng Siu-Ping, Alves Derron A, Tirloni Lucas, Anderson Jennifer M, Oliveira Fabiano, Kamhawi Shaden, Sonenshine Daniel E, Marques Adriana, Ribeiro José M C, Hoon Mark, Valenzuela Jesus G
bioRxiv. 2025 Aug 28:2025.08.22.671835. doi: 10.1101/2025.08.22.671835.
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.
获得性蜱抗性（ATR）在蜱暴露动物中已有充分表征，其通过抗体介导的嗜碱性粒细胞激活来损害蜱的适应性。然而，诱导ATR的抗蜱疫苗成效有限。在此，我们描述了ATR之前发生的一种神经免疫事件，该事件会导致宿主迅速介导蜱的清除。蜱致敏的豚鼠通过获得性神经免疫诱导的瘙痒反应，在3至6小时内机械性地清除蜱，这种反应与瘙痒相关基因（如OSM）的皮肤表达增加以及T细胞和巨噬细胞的皮肤浸润相关，且与IgG和IgE抗体无关。当我们让人类接触蜱时，会观察到类似的免疫反应。在蜱致敏前阻断T细胞可防止免疫细胞浸润到叮咬部位，并消除抓挠和蜱的清除。这种神经免疫反应独立于瞬时受体电位香草酸亚型1（Trpv1），因为用树脂毒素处理的蜱致敏豚鼠能有效清除蜱。瘙痒诱导的蜱清除（IITR）通过早期蜱的检测和清除，为蜱传疾病的预防提供了一种新方法。
