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。感染是通过摄入含有感染性第三期幼虫的胚胎卵而获得的。这些幼虫在被宿主摄入后孵化，通过肠系膜静脉到达肝脏，并在肝脏组织内停留，直到它们通过血液继续迁移到肺部。幼虫通过肺泡迁移后，经气管到达口腔，随后被吞下。因此，它们在感染后约4周到达胃肠道，进入成虫前期，最后进入性成熟成虫，并通过产生大量卵来完成生命周期。受感染的猪最常见的表现是非特异性的临床症状，如生产性能下降和生长迟缓。在宿主体内，猪蛔虫的发展已经得到了很好的描述；然而，这种寄生虫的作用机制尚不清楚。很少有来自猪和蛋鸡的研究数据表明猪蛔虫对肠道营养物质运输机制的影响。因此，该项目的目的是研究猪蛔虫感染对葡萄糖、氨基酸和二肽肠道运输的影响。此外，由于这些抗原与肠壁直接接触，因此将评估寄生虫的排泄-分泌抗原和表皮抗原对这些运输机制的影响。通过电生理反应对粘膜添加营养物质后的完整上皮进行体外测量分析。此外，还将采用放射性标记的底物测量营养通量率，并对肠细胞的管腔膜和基底外膜的膜囊进行摄取研究。分子方法包括定量实时PCR、免疫印迹和免疫组织化学来评估转运体系统的转录和表达，将完成功能分析。预期的见解不仅有助于更好地了解宿主-寄生虫的相互作用，而且还将为新的创新治疗方法提供基础。除了针对猪或人蛔虫病吸收不良的治疗干预外，这也可能包括潜在的目标分子识别，有助于开发治疗病因不同的吸收障碍或肥胖的治疗方法。这就排除了肠道营养转运系统对猪单胞菌感染反应的完整功能表征，这将由计划中的项目实现。

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.