Dual oxidase 2 and glutathione peroxidase gene expression are elevated in hyperimmunized sheep challenged with...

A sequential biopsy sampling method was used to investigate oxidant and antioxidant gene responses in resistant sheep challenged with Haemonchus contortus larvae or a sham saline challenge. The expression of key sheep oxidant and antioxidant producing genes were measured in sequential samples removed from the abomasums at days 0, 1, 2, 3, 5, 7 and 28 post challenge. Gene expression levels at each time point were compared to expression at day 0, and levels of the various genes were also correlated to other markers of infection including immune cell counts and cytokine gene expression. The early response to larval challenge infection in resistant animals was marked by a divergence of two groups of host oxidant producing genes: the dual oxidase group (DUOX2/DUOXA2) showing increases in expression to day 7, while members of the phagocytic NADPH oxidase (PHOX) group showed significant decreases in expression. The change in DUOX2 expression between days zero and seven, when host resistance to infection is mediated, was negatively correlated to final worm burden suggesting NADPH oxidase expression may play a role in parasite expulsion. Expression of the DUOX group oxidants was positively correlated to expression of the Th2 cytokine IL4. Changes in host antioxidant pathways between different members of the glutathione peroxidase family (intestinal and plasma GPX) and genes involved in glutathione metabolism were also observed. This first study of the putative roles of oxidant production by the dual oxidase group, antioxidant glutathione pathways, immune cell populations, and cytokine profiles, in the development of resistance to infection by hyperimmune sheep are discussed.