Departamento de Biología, Universidad de Guanajuato, Guanajuato, Mexico.
Departamento de Ingenierías Química, Electrónica y Biomédica, Universidad de Guanajuato, Guanajuato, Mexico.
Parasitology. 2019 Nov;146(13):1636-1645. doi: 10.1017/S0031182019001094. Epub 2019 Aug 28.
Trichomonas vaginalis is an extracellular parasite that colonizes the human urogenital tract leading to trichomoniasis, the most common sexually-transmitted non-viral disease worldwide. The immune response plays a critical role in the host defense against this parasite. Trichomonas' DNA contains unmethylated CpG motifs (CpGDNA) that in other microorganisms act as modulators of the immune response. However, the molecular mechanisms responsible for CpGDNA immune modulation are still unclear. As macrophages participate in the first line of defense against infection, we investigated the type of immune response of murine macrophages to T. vaginalis DNA (TvDNA). We observed high expression of the proinflammatory cytokines IL-6 and IL-12p40 in macrophages stimulated with TvDNA. In contrast, the anti-inflammatory response, assessed by IL-10 and IL-13 mRNA expression was delayed. This suggests that the immune response induced by TvDNA is modulated through cytokine production, mediated partly by NADPH-oxidase activity, as TvDNA induced reactive species of oxygen production and a rounded morphology in macrophages indicative of an M1 phenotype. Furthermore, infected mice pretreated with TvDNA displayed persistent vulvar inflammation and decreased parasite viability consistent with higher proinflammatory cytokine levels during infection compared to untreated mice. Overall, our findings suggest that TvDNA pretreatment modulates the immune response favouring parasite elimination.
阴道毛滴虫是一种寄生于人体泌尿生殖道的细胞外寄生虫，可引起滴虫病，这是全球最常见的性传播非病毒性疾病。免疫反应在宿主抵御这种寄生虫方面起着至关重要的作用。阴道毛滴虫的 DNA 含有未甲基化的 CpG 基序（CpGDNA），在其他微生物中，CpGDNA 作为免疫反应的调节剂。然而，负责 CpGDNA 免疫调节的分子机制尚不清楚。由于巨噬细胞参与了感染的第一道防线，我们研究了鼠巨噬细胞对阴道毛滴虫 DNA（TvDNA）的免疫反应类型。我们观察到，用 TvDNA 刺激的巨噬细胞中促炎细胞因子 IL-6 和 IL-12p40 的表达水平较高。相比之下，通过 IL-10 和 IL-13 mRNA 表达评估的抗炎反应则延迟。这表明 TvDNA 诱导的免疫反应通过细胞因子产生进行调节，部分通过 NADPH 氧化酶活性进行调节，因为 TvDNA 诱导了巨噬细胞中活性氧的产生和圆形形态，表明其为 M1 表型。此外，用 TvDNA 预处理感染的小鼠表现出持续的外阴炎症和寄生虫活力降低，与未经处理的小鼠相比，感染期间促炎细胞因子水平升高。总的来说，我们的研究结果表明，TvDNA 预处理可调节免疫反应，有利于寄生虫的清除。
