|Van den broeck, W|
Submitted to: Infection and Immunity
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/2/2013
Publication Date: 3/11/2013
Citation: Van, M., Van, C., Borloo, J., Rinaldi, M., Li, R.W., Chiers, K., Van Den Broeck, W., Vercruysse, J., Claerebout, E., Geldhof, P. 2013. Granule-exocytosis of granulysin and granzyme B as a potential key mechanism in vaccine-induced immunity in cattle against the nematode ostertagia ostertagi. Infection and Immunity. 81(15):1798-1809. Interpretive Summary: Gastrointestinal nematodes have major economic consequences that result in a significant loss to cattle farmers worldwide. Immunological control of nematode infections through vaccination is often regarded as the most rational and cost-effective method to control parasitic infections in livestock. The characterization of abomasal immune responses of vaccinated animals following a trickle infection is reported. Several genes, including granulysin, granzyme B and IgE receptor 506 subunit A were identified as potentially important elements in the development of immunity against the abomasal nematode Ostertagia ostertagi in cattle. The knowledge obtained will facilitate the development of more effective vaccines.
Technical Abstract: Ostertagia ostertagi is considered one of the most economically important bovine parasites. As an alternative for anthelmintic treatment, an experimental host-protective vaccine was previously developed based on ASP-proteins derived from the adult worms. Intramuscular injection of this vaccine, combined with QuilA as adjuvant, significantly reduced the faecal egg counts by 74%. However, the immunological mechanisms triggered by the vaccine are still unclear. Therefore, in this study, the differences in immune responses at the site of infection, i.e. the abomasal mucosa, between ASP/QuilA33 vaccinated animals and QuilA-vaccinated control animals were investigated on a transcriptomic level, using a whole genome bovine micro-array, combined with histological analysis. Sixty nine genes were significantly impacted in animals protected by the vaccine, 48 of which were upregulated. A correlation study between the parasitological parameters and gene transcription levels showed that the transcription levels of two of the upregulated genes, granulysin (GNLY) and granzyme B (GZMB)negatively correlated to cumulative faecal egg counts and total worm counts,respectively. Both genes also positively correlated to each other, and to another upregulated gene, the IgE receptor subunit FCER1A. Surprisingly, these three genes also correlated significantly to CMA1, a mast cell marker, and to cell counts for mast cells and cells previously described as globule leukocytes. Furthermore, immunohistochemical data showed that GNLY was present in the granules of globule leukocytes and that it was secreted in the mucus. Overall, the results suggest a potential role of granule exocytosis by globule leucocytes, potentially IgE-mediated, in the vaccine induced protection against O. ostertagi.