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[Erscheinungsort nicht ermittelbar]: Trinity College Dublin. School of Natural Sciences. Discipline of Zoology, 2020
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Dissertation, Trinity College Dublin. School of Natural Sciences. Discipline of Zoology, 2020
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APPROVED ; The parasitic nematode Ascaris lumbricoides infects 800 million people worldwide. The age group most affected by this parasite are children between the ages of 5 and 15 years. The symptoms of ascariasis can be broadly divided into acute and chronic. The acute symptoms are more severe, but relatively rare. It is in fact the chronic symptoms that are more common, but less severe. The impact of these chronic symptoms, which include malnutrition and diminished cognitive development, can however, not be underestimated, as these contribute to the significant morbidity associated with ascariasis. Severity of disease is linked to the number of worms a host harbours, with some people harbouring heavy infections whereas other only experience light infections with few worms. People that are found to have heavy infections, tend to regain similar high worm burdens upon reinfection, even after several rounds of chemotherapy. The reasons why some people harbour many worms, and others only few, are unknown. This body of work aims to elucidate some of the mechanisms behind this difference. The porcine ascarid, Ascaris suum, has been used previously to develop a mouse model where one mouse strain is a model for heavy infection and the other mouse strain is a model for light infection. Using this model, previous work was able to identify the liver stage of the parasitic life cycle as the likely stage at which this difference in infection rate occurs. Chapter 2 is a review of the available literature of the importance of the liver as an organ during parasite migration. It investigates the incorporation of the liver in the life cycle of three parasites of global significance: Ascaris, Schistosoma, and Plasmodium. In chapter 3, the mouse model is used to investigate the differences between the livers of the two mouse strains during A. suum infection, from a proteomics perspective. The results show that there are some important intrinsic differences between the two mouse strains, with the relatively resistant mouse strain having a higher abundance in proteins involved in oxidative phosphorylation and complement activation. Building on the mouse model, chapter 4 explores the potential for this model to be used to examine the human ascarid A. lumbricoides. Due to relative ease of obtaining A. suum eggs, this has so far been the preferred parasite, but little research has been performed to investigate if there are any differences in a mouse model between these two parasites. This chapter thus concludes that resistance and susceptibility in the mouse model, as observed in A. suum infection, are retained for A. lumbricoides infection and therefore that A. lumbricoides is suitable for use in this model. The final data chapter, chapter 5, focusses on the hepatic immune response against A. suum and A. lumbricoides in this mouse model. These results indicate that at the investigated time point, of day 7 post infection, the innate immune system plays an important role, more specifically the eosinophils, dendritic cells and monocytes. This was found to be true for both ascarid species and for both mouse strains. In all, this body of work has contributed novel data on the understudied aspect of the hepatic resistance to Ascaris infection in a mouse model.