Rhipicephalus microplus ticks feed on a bovine host for three weeks. At the attachment site, inflammatory and immune responses are triggered resulting in the recruitment of cells and production of a set of immunological mediators. To oppose the host’s immune responses, ticks inoculate bioactive salivary molecules capable of interfering with these defense mechanisms. Serpins are among the most frequent molecules present in tick saliva and have been shown to negatively affect the host’s anti-tick immunity. R. microplus has at least eighteen full-length serpins (RmS) and eleven are transcribed during blood feeding. Among them, RmS-3, RmS-6, and RmS-17 are present in the saliva of engorged females. Here, the effect of these serpins on the immune responses was evaluated in cells involved in innate/inflammatory (mast cells and macrophages) and adaptive (T cells) immunity. RmS-3 modulated mast cells due to its inhibitory activity on peritoneal rat chymase and on vascular permeability in acute inflammation. In addition, both RmS-6 and RmS-17 inhibited vascular permeability. Of the three serpins studied, neither affected activation nor inflammatory cytokine production by murine macrophages. On the other hand, RmS-3 and RmS-17 presented an inhibitory effect on the metabolic activity of lymphocytes, with the latter being the most potent, while RmS-6 had no effect on it. This activity was associated with a decrease in lymphocyte proliferation, but not with induction of cell death. The present study highlights the powerful modulatory role of tick salivary serpins in the host’s immune system and inspire the discovery of targets for the treatment of inflammatory/immune disorders.

微小扇头蜱以牛宿主为食三周。在附着位点，炎症和免疫反应被触发，导致细胞的募集和一组免疫介质的产生。为了对抗宿主的免疫反应，蜱虫会接种能够干扰这些防御机制的生物活性唾液分子。丝氨酸蛋白酶抑制剂是蜱唾液中最常见的分子之一，已被证明会对宿主的抗蜱免疫力产生负面影响。 R. microplus至少有 18 个全长丝氨酸蛋白酶抑制剂 (RmS)，其中 11 个是在吸血期间转录的。其中，RmS-3、RmS-6和RmS-17存在于充血雌性的唾液中。在这里，在参与先天/炎症（肥大细胞和巨噬细胞）和适应性（T 细胞）免疫的细胞中评估了这些丝氨酸蛋白酶抑制剂对免疫反应的影响。 RmS-3 由于其对腹膜大鼠食糜酶和急性炎症中血管通透性的抑制活性而调节肥大细胞。此外，RmS-6和RmS-17均抑制血管通透性。在所研究的三种丝氨酸蛋白酶抑制剂中，既不影响小鼠巨噬细胞的激活也不影响炎症细胞因子的产生。另一方面，RmS-3和RmS-17对淋巴细胞的代谢活性有抑制作用，其中后者最强，而RmS-6则无影响。这种活性与淋巴细胞增殖的减少有关，但与细胞死亡的诱导无关。本研究强调了蜱唾液丝氨酸蛋白酶抑制剂在宿主免疫系统中的强大调节作用，并激发了炎症/免疫性疾病治疗靶点的发现。