Analysis of cell hyperplasia and parietal cell dysfunction induced by Ostertagia ostertagi infection.

Infections in cattle with the gastric nematode Ostertagia ostertagi are associated with decreased acid secretion and profound physio-morphological changes of the gastric mucosa. The purpose of the current study was to investigate the mechanisms triggering these pathophysiological changes. O. ostertagi infection resulted in a marked cellular hyperplasia, which can be explained by increased transcriptional levels of signaling molecules related to the homeostasis of gastric epithelial cells such as HES1, WNT5A, FGF10, HB-EGF, AREG, ADAM10 and ADAM17. Intriguingly, histological analysis indicated that the rapid rise in the gastric pH, observed following the emergence of adult worms, cannot be explained by a loss of parietal cells, as a decrease in the number of parietal cells was only observed following a long term infection of several weeks, but is likely to be caused by an inhibition of parietal cell activity. To investigate whether this inhibition is caused by a direct effect of the parasites, parietal cells were co-cultured with parasite Excretory/Secretory products (ESP) and subsequently analyzed for acid production. The results indicate that adult ESP inhibited acid secretion, whereas ESP from the L4 larval stages did not alter parietal cell function. In addition, our data show that the inhibition of parietal cell activity could be mediated by a marked upregulation of inflammatory factors, which are partly induced by adult ESP in abomasal epithelial cells. In conclusion, this study shows that the emergence of adult O. ostertagi worms is associated with marked cellular changes that can be partly triggered by the worm's Excretory/secretory antigens.

Evidence for a parasite-mediated inhibition of abomasal acid secretion in sheep infected with Ostertagia leptospicularis.

The acid secretory capacity of the abomasal mucosa was studied in sheep experimentally infected with Ostertagia leptospicularis. The acidity of the abomasal contents, permanently recorded by a pH probe located inside the abomasum, decreased markedly to mean levels between pH 5 and 6. Subcutaneous administration of histamine or carbachol successfully stimulated acid secretion (pH 3.4). The results indicate that the abomasal mucosa harboured a population of functional parietal cells which were also identified immunohistochemically (H(+)/K(+)-ATPase). Ultrastructural investigation before stimulation revealed that the majority of these cells was in a resting state. Despite high serum gastrin levels, the acid secretion was blocked either at the level of the parietal cell or the enterochromaffin-like cell by an unknown factor, possibly mediated by the parasites. This is the first report of a parietal cell dysfunction associated with a nematode infection in the abomasum. It is suggested that the parasites induce changes in their environment which favour their survival and/or increase their reproduction.