Large roundworm induced malabsorption: modulation of intestinal porcine nutrient transport

猪蛔虫是欧洲养猪业中最重要的寄生虫。通过摄入含有感染性第三阶段幼虫的含胚卵而获得感染。这些幼虫在被宿主摄入后孵化，通过肠系膜静脉到达肝脏，并在组织嗜性期期间留在肝脏组织内，直到它们通过血流继续迁移到肺中。在通过肺泡迁移后，幼虫通过气管到达口腔，随后被吞咽。因此，它们在感染后约4周到达胃肠道，在那里它们发育成成虫前期，最后发育成性成熟的成虫，并通过产生大量的卵来完成生命周期。受感染的猪最常表现出非特异性的临床症状，如性能下降和生长迟缓。在宿主体内，猪蛔虫的发展已被很好地描述;然而，这种寄生虫的作用机制大多是未知的。从猪以及包括产蛋鸡的研究中获得的数据很少表明猪蛔虫对肠道营养转运机制的影响。因此，本项目的目的是研究猪蛔虫感染对肠道葡萄糖、氨基酸和二肽转运的影响。此外，将评价寄生虫排泄分泌抗原以及表皮抗原对这些转运机制的影响，因为这些抗原与肠壁直接接触。通过电生理反应向粘膜添加营养物后，将利用完整上皮的体外测量值进行分析。此外，将采用放射性标记底物测量营养素通量率，并进行肠细胞腔和基底外侧膜膜囊泡的摄取研究。包括定量实时PCR，免疫印迹和免疫组织化学的分子方法来评估转运系统的转录和表达将完成功能分析。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中吸收不良的治疗干预之外，这还可以包括对有助于开发用于治疗病因学上不同的吸收障碍或肥胖症的治疗剂的靶分子的潜在鉴定。这就排除了肠内营养转运系统对A.猪感染，这将通过计划的项目实现。

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.