Laboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos - UFSCar, São Carlos, Brazil.
Departamento de Biologia Animal, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, Brazil.
Front Immunol. 2020 Sep 23;11:569988. doi: 10.3389/fimmu.2020.569988. eCollection 2020.
Schistosomiasis, caused by trematode worm, affects more than 1.5 million people in Brazil. The current treatment consists in the administration of Praziquantel, the only medicine used for treatment for more than 40 years. Some of the limitations of this drug consist in its inactivity against schistosomula and parasite eggs, the appearance of resistant strains and non-prevention against reinfection. Thus, the objective of this study was to evaluate the effect of immunization with recombinant functional enzymes of the purine salvage pathway of , Nucleoside Diphosphate Kinase (NDPK) and Adenylosuccinate Lyase (ADSL), to evaluate the host immune response, as well as the parasite load after vaccination. For this, Balb/c mice were divided into 5 groups: control (uninfected and untreated), non-immunized/infected, NDPK infected, ADSL infected, and NDPK + ADSL infected. Immunized groups received three enzyme dosages, with a 15-day interval between each dose, and after 15 days of the last application the animals were infected with 80 cercariae of . On the 47th day after the infection, fecal eggs were counted and, on the 48th day after the infection, the evaluation of leukocyte response, parasite load, antibody production, cytokines quantification, and histopathological analysis were performed. The results showed that immunizations with NDPK, ADSL or NDPK + ADSL promoted a discreet reduction in eosinophil counts in lavage of peritoneal cavity. All immunized animals showed increased production and secretion of IgG1, IgG2a, and IgE antibodies. Increased production of IL-4 was observed in the group immunized with the combination of both enzymes (NDPK + ADSL). In addition, in all immunized groups there were reductions in egg counts in the liver and intestine, such as reductions in liver granulomas. Thus, we suggest that immunizations with these enzymes could contribute to the reduction of schistosomiasis transmission, besides being important in immunopathogenesis control of the disease.
血吸虫病是由吸虫引起的,在巴西影响着超过 150 万人。目前的治疗方法是使用吡喹酮,这是一种 40 多年来唯一用于治疗的药物。这种药物的一些局限性在于它对尾蚴和寄生虫卵无效,出现耐药株以及不能预防再感染。因此,本研究的目的是评估用嘌呤补救途径的重组功能酶(核苷二磷酸激酶(NDPK)和腺苷酸琥珀酸裂解酶(ADSL))进行免疫接种的效果,以评估宿主免疫反应以及接种后的寄生虫负荷。为此,将 Balb/c 小鼠分为 5 组:对照组(未感染和未治疗)、非免疫/感染组、NDPK 感染组、ADSL 感染组和 NDPK+ADSL 感染组。免疫组接受了三种酶剂量,剂量之间间隔 15 天,最后一次给药后 15 天,动物感染 80 条尾蚴。在感染后第 47 天,计算粪便中的虫卵数,在感染后第 48 天,评估白细胞反应、寄生虫负荷、抗体产生、细胞因子定量和组织病理学分析。结果表明,用 NDPK、ADSL 或 NDPK+ADSL 免疫接种可轻微减少腹腔灌洗中的嗜酸性粒细胞计数。所有免疫动物均表现出 IgG1、IgG2a 和 IgE 抗体产生和分泌增加。在联合使用两种酶(NDPK+ADSL)的免疫组中观察到 IL-4 产生增加。此外,在所有免疫组中,肝和肠中的虫卵计数均减少,肝肉芽肿也减少。因此,我们认为用这些酶进行免疫接种可能有助于减少血吸虫病的传播,同时对疾病的免疫发病机制控制也很重要。