Large roundworm induced malabsorption: modulation of intestinal porcine nutrient transport

大蛔虫引起的吸收不良：猪肠道营养运输的调节

• 批准号: 402837808
• 负责人: Professor Dr. Gerhard Breves
• 金额: --
• 依托单位: Institut für Parasitologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/402837808?language=en
• 关键词: Large; roundworm; induced; malabsorption; modulation

The roundworm Ascaris suum is the most important parasite in pig farming in Europe. Infections are acquired by ingestion of embryonated eggs containing the infective third-stage larva. These larvae hatch after ingestion by the host, reach the liver via the mesenteric veins and remain within the liver tissue during a histotropic phase until they continue migration via blood stream into the lungs. Following migration through alveoli, larvae reach the oral cavity via the trachea and are subsequently swallowed. Thus, they reach the gastrointestinal tract about 4 weeks post infection, where they develop into the preadult stage and finally into sexually mature adults and complete the life cycle by producing large amounts of eggs. Infected pigs most commonly show unspecific clinical signs like decreased performance and retardation of growth. Within the host, the development of Ascaris suum has well been described; however, mechanisms of action of this parasite are mostly unknown. Few data obtained from pigs as well as studies comprising laying hens indicate an influence of Ascaris suum on intestinal nutrient transport mechanisms. Therefore, the aim of the project is the investigation of the effect of an Ascaris suum-infection in pigs on intestinal transport of glucose, amino acids and dipeptides. Additionally, the effect of excretory-secretory antigens as well as cuticle antigens of the parasite on these transport mechanisms will be evaluated as these antigens are in direct contact with the intestinal wall. Analyses will be conducted utilizing in vitro-measurements of the intact epithelium after mucosal addition of nutrients via electrophysiological response. Furthermore, measurements on nutrient flux rates employing radioactively labeled substrates as well as uptake studies into membrane vesicles of luminal and basolateral membranes of enterocytes will be conducted. Molecular approaches comprising quantitative real-time PCR, immunoblotting and immunohistochemistry to evaluate transcription and expression of transporter systems will complete the functional analyses. The expected insights will not only contribute to a better understanding of the host-parasite interactions, but will also provide the basis for new, innovative therapeutic approaches. Beside therapeutic intervention concerning malabsorption in porcine or human ascariosis, this may also include the potential identification of target molecules contributing to the development of therapeutics for the treatment of etiologically different absorption disorders or obesity. This precludes the complete functional characterization of intestinal nutrient transport systems in response to A. suum infections, which will be achieved by the planned project.

猪蛔虫是欧洲养猪业最重要的寄生虫。感染是通过摄入含有感染第三阶段幼虫的胚胎卵子而获得的。这些幼虫在被宿主摄食后孵化，通过肠系膜静脉到达肝脏，并在组织趋化期留在肝脏组织中，直到它们通过血液继续迁移到肺部。幼虫通过肺泡迁徙后，通过气管到达口腔，随后被吞噬。因此，它们在感染后大约4周到达胃肠道，在那里发育到成虫前阶段，最终成年性成熟，并通过产生大量卵子完成生命周期。受感染的猪通常表现出非特异性的临床症状，如生产性能下降和生长迟缓。在宿主内部，猪蛔虫的发育已经被很好地描述，然而，这种寄生虫的作用机制大多是未知的。从猪身上获得的数据以及包括蛋鸡在内的研究表明，猪蛔虫对肠道养分运输机制的影响很少。因此，该项目的目的是调查猪蛔虫感染对葡萄糖、氨基酸和二肽在肠道中转运的影响。此外，由于寄生虫的排泄-分泌抗原和角质层抗原与肠壁直接接触，因此将评估这些抗原对这些转运机制的影响。分析将利用体外测量，通过电生理反应在粘膜添加营养物质后对完整的上皮进行测量。此外，还将使用放射性标记底物测量营养通量，并对肠细胞腔和基侧膜的膜囊进行摄取研究。包括实时定量聚合酶链式反应、免疫印迹和免疫组织化学在内的评估转运蛋白系统转录和表达的分子方法将完成功能分析。预期的见解不仅有助于更好地了解宿主-寄生虫的相互作用，而且还将为新的创新治疗方法提供基础。除了关于猪或人蛔虫病吸收不良的治疗干预外，这还可能包括潜在的靶标分子的鉴定，这些靶分子有助于开发治疗不同原因的吸收障碍或肥胖的治疗方法。这排除了对猪链霉菌感染反应的肠道营养运输系统的完整功能表征，这将通过计划的项目实现。