Ferreira B R, Silva J S
Department of Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Vet Immunol Immunopathol. 1998 Jul 31;64(3):279-93. doi: 10.1016/s0165-2427(98)00135-4.
In this study, we investigated tick saliva effects on T cell proliferation, antigen presentation and IFN-gamma-induced macrophage activation, events which are associated with host immune defense mechanisms. Mice repeatedly infested with Rhipicephalus sanguineus ticks, similarly to dogs, did not develop resistance to further infestations. We determined that R. sanguineus tick saliva inhibited, in a dose-dependent manner, both Con-A and specific antigen-induced splenic T cell proliferation. Tick saliva diluted twenty times (64 microg/ml) inhibited Con-A-induced and antigen-specific T cell proliferation in 83% and 69%, respectively. In addition, the inhibition of cell proliferation correlated with a decrease in IL-2 production. Microconcentrator fractionated saliva was tested on a Con-A-induced cell proliferation assay, and showed that one fraction between 3 and 10 kDa and another smaller than 3 kDa can be responsible for the inhibition of T cell proliferation. Although saliva inhibited cell proliferation, it did not impair antigen presentation. Tick saliva further abrogated the killing of intracellular forms of Trypanosoma cruzi by IFN-gamma-activated macrophages. Moreover, saliva-induced macrophage inhibition of IFN-gamma-induced-trypanocidal activity was paralleled with 69% less nitric oxide (NO) production. Finally, tick saliva doubled the production of IL-10 and reduced 84.6% production of IFN-gamma by splenocytes cultured with T. cruzi, suggesting that decreased macrophage NO production may be due to a saliva-induced cytokine imbalance, leading to decreased NO synthase activity. Together, these data indicate that tick saliva can modulate host immune response, thus, contributing to its feeding success and favoring the transmission of tick-borne pathogens.
在本研究中，我们调查了蜱唾液对T细胞增殖、抗原呈递以及干扰素-γ诱导的巨噬细胞活化的影响，这些事件与宿主免疫防御机制相关。与犬类相似，多次感染血红扇头蜱的小鼠并未对进一步感染产生抗性。我们确定，血红扇头蜱唾液以剂量依赖的方式抑制了刀豆蛋白A（Con-A）和特异性抗原诱导的脾T细胞增殖。稀释20倍（64微克/毫升）的蜱唾液分别抑制了83%的Con-A诱导的和69%的抗原特异性T细胞增殖。此外，细胞增殖的抑制与白细胞介素-2（IL-2）产生的减少相关。在Con-A诱导的细胞增殖试验中测试了微浓缩器分级分离的唾液，结果表明分子量在3至10千道尔顿之间的一个组分以及另一个小于3千道尔顿的组分可能是抑制T细胞增殖的原因。尽管唾液抑制了细胞增殖，但它并未损害抗原呈递。蜱唾液进一步消除了干扰素-γ激活的巨噬细胞对克氏锥虫细胞内形式的杀伤作用。此外，唾液诱导的巨噬细胞对干扰素-γ诱导的杀锥虫活性的抑制与一氧化氮（NO）产生减少69%平行。最后，蜱唾液使与克氏锥虫共培养的脾细胞产生的IL-10增加了一倍，并使干扰素-γ的产生减少了84.6%，这表明巨噬细胞NO产生减少可能是由于唾液诱导的细胞因子失衡，导致一氧化氮合酶活性降低。总之，这些数据表明蜱唾液可以调节宿主免疫反应，从而有助于其取食成功并有利于蜱传播病原体。
