Host-parasite interactions during abomasal parasitism and potential roles for ES products : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand

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Massey University
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Parasite excretory/secretory (ES) products are believed to play a role in the initiation of the host response to the abomasal parasites Haemonchus contortus and Teladorsagia circumcincta. Both parasites inhibit and cause loss of the acid-producing parietal cells. Three days after transplantation of adult T. circumcincta into parasite-naive sheep, a subpopulation of their parietal cells no longer expressed the proton pump β-subunit, but still stained for Transforming Growth Factor-α, suggesting loss of the proton pump preceded cell death. To investigate the ability of parasites to modify the function of mammalian cells in vitro, HeLa, AGS and CaCo-2 cells were exposed to ES products. ES products vacuolated all three cells, causing the development of large numbers of small vacuoles, which differed in appearance from those produced by Helicobacter pylori bacterial toxin VacA or ammonia. The vacuoles were unlike those which develop in parietal cells in the parasitised abomasum. Neither lipids nor prostaglandins appeared to play a role in vacuolation and the vacuolating factor in vitro is likely to be a protein because of its heat and acid lability. Vacuolation occurred within one hour and was partially reversible. ES products were also able to cause cytoskeletal rearrangement and detachment of HeLa cells, similar processes to those caused by bacterial pathogens, which also disrupt tight junctions in mammalian cells. H. contortus ES products also disrupted tight junctions of CaCo-2 cell monolayers, a model cell system used for these studies. The increased epithelial permeability was associated with structural rearrangements of the tight junction proteins occludin and ZO-1. This could explain protein loss and back-diffusion of pepsinogen into the blood, a marker of abomasal parasitism. Cell detachment and disruption of cell-cell adhesion in parasitised sheep may inhibit acid production by parietal cells, which cannot function when separated from adjacent cells. Increased permeability of the surface epithelium would allow parasite ES products to penetrate the mucosal barrier, causing further damage. This could also allow inhibition of parietal cells deeper in the abomasal glands and also allowing adult parasites living in the gastric lumen to modulate host immunity to enhance their survival.
Sheep, Parasites, Excretory/secretory products, ES products, Haemonchus contortus, Teladorsagia circumcincta