de Lima Fragelli Bruna Dias, Fattori Ana Carolina Maragno, de Almeida Montija Elisandra, de Almeida Rodolpho Joice Margareth, de Castro Cynthia Aparecida, de Godoy Krissia Franco, Nogueira Camila Tita, Rodrigues Vanderlei, Soares Edson Garcia, Romanello Larissa, Torini Juliana R, Pereira Humberto D'Muniz, de Freitas Anibal Fernanda
Laboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, São Carlos 13565-905, Brazil.
Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil.
Pathogens. 2023 Mar 29;12(4):527. doi: 10.3390/pathogens12040527.
Schistosomiasis is a parasitic infection caused by trematode worms (also called blood flukes) of the genus sp., which affects over 230 million people worldwide, causing 200,000 deaths annually. There is no vaccine or new drugs available, which represents a worrying aspect, since there is loss of sensitivity of the parasite to the medication recommended by the World Health Organization, Praziquantel. The present study evaluated the effects of the recombinant enzymes of Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT), Purine Nucleoside Phosphorylase (PNP) and the MIX of both enzymes in the immunotherapy of schistosomiasis in murine model. These enzymes are part of the purine salvage pathway, the only metabolic pathway present in the parasite for this purpose, being essential for the synthesis of DNA and RNA. Female mice of Swiss and BALB/c strains were infected with cercariae and treated, intraperitoneally, with three doses of 100 µg of enzymes. After the immunotherapy, the eggs and adult worms were counted in the feces; the number of eosinophils from the fluid in the peritoneal cavity and peripheral blood was observed; and the quantification of the cytokine IL-4 and the production of antibodies IgE was analyzed. The evaluation of the number of granulomas and collagen deposition via histological slides of the liver was performed. The results demonstrate that immunotherapy with the enzyme HGPRT seems to stimulate the production of IL-4 and promoted a significant reduction of granulomas in the liver in treated animals. The treatment with the enzyme PNP and the MIX was able to reduce the number of worms in the liver and in the mesenteric vessels of the intestine, to reduce the number of eggs in the feces and to negatively modulate the number of eosinophils. Therefore, immunotherapy with the recombinant enzymes of HGPRT and PNP might contribute to the control and reduction of the pathophysiological aspects of schistosomiasis, helping to decrease the morbidity associated with the infection in murine model.
血吸虫病是由裂体吸虫属的吸虫（也称为血吸虫）引起的寄生虫感染，全球有超过2.3亿人受其影响，每年导致20万人死亡。目前尚无可用的疫苗或新药，这是一个令人担忧的问题，因为寄生虫对世界卫生组织推荐的药物吡喹酮产生了耐药性。本研究评估了次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）、嘌呤核苷磷酸化酶（PNP）的重组酶以及两种酶的混合物在小鼠血吸虫病免疫治疗中的作用。这些酶是嘌呤补救途径的一部分，是寄生虫中唯一用于此目的的代谢途径，对DNA和RNA的合成至关重要。将瑞士和BALB/c品系的雌性小鼠感染尾蚴，并通过腹腔注射给予三剂100μg的酶进行治疗。免疫治疗后，对粪便中的虫卵和成虫进行计数；观察腹腔液和外周血中嗜酸性粒细胞的数量；分析细胞因子IL-4的定量和抗体IgE的产生。通过肝脏组织切片评估肉芽肿数量和胶原沉积。结果表明，用酶HGPRT进行免疫治疗似乎能刺激IL-4的产生，并使治疗动物肝脏中的肉芽肿显著减少。用酶PNP和混合物进行治疗能够减少肝脏和肠道肠系膜血管中的虫体数量，减少粪便中的虫卵数量，并对嗜酸性粒细胞数量产生负调节作用。因此，用HGPRT和PNP的重组酶进行免疫治疗可能有助于控制和减少血吸虫病的病理生理方面，有助于降低小鼠模型中与感染相关的发病率。
