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Title: Micro array analysis of the intestinal host response in Giardia duodenalis assemblage E infected cattle

Author
item DREESEN, L - Ghent University
item RINALDI, M - Ghent University
item CHIERS, K - Ghent University
item Li, Robert
item GEURDEN, T - Ghent University
item VAN DEN BROECK, W - Ghent University
item GODDEERIS, B - Ghent University
item VERCRUYSSE, J - Ghent University
item CLAEREBOUT, E - Ghent University
item GELDHOF, P - Ghent University

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/15/2012
Publication Date: 7/27/2012
Citation: Dreesen, L., Rinaldi, M., Chiers, K., Li, R.W., Geurden, T., Van Den Broeck, W., Goddeeris, B., Vercruysse, J., Claerebout, E., Geldhof, P. 2012. Micro array analysis of the intestinal host response in Giardia duodenalis assemblage E infected cattle. PLoS One. 7(7):e40985.

Interpretive Summary: The protozoan parasite Giardia duodenalis is one of the most commonly found intestinal pathogens in a wide range of vertebrate hosts, including both farm and companion animals. Approximately 280 million people are infected with this parasite annually, especially in developing countries. The symptoms generally include diarrhea, malnutrition, growth impairment, and poor cognitive development, although the majority of the infections remain asymptomatic and, therefore, unnoticed. Studies have shown that prevalence can be as high as 100 % in certain cattle and sheep farms. In this study, we investigated molecular changes in global gene expression profiles in the gut of calves as well as histological alterations induced by the infection. Results suggested a reduction in the immune defenses of infected calves compared to normal uninfected calves. Knowledge obtained from this study will facilitate the development of means to reduce chronic Giardia infections, which will benefit a significant portion of the population in developing countries and animal farmers around the world.

Technical Abstract: Giardia duodenalis is one of the most commonly found intestinal pathogens in humans and animals. However, little is known about the host-parasite interaction in its natural hosts. The objective of this study was to investigate the intestinal response in calves following a G. duodenalis infection, using a bovine high-density oligo microarray to analyze global gene expression in the small intestine. Our microarray data results suggest a decrease in inflammation, immune response, and immune cell migration in infected animals, which was examined in more detail by quantitative real-time PCR on a panel of cytokines combined with histological analyses. The cytokine transcription levels showed a trend of down regulated expression in infected animals compared to the negative controls, best seen in the jejunum for IL-6 and IL-8 and statistically significant for IL-17, IL-13 and IFN-'. No increased immune cell recruitment could be seen after infection, as well as no intestinal pathologies, such as villi shortening or increased levels of apoptosis. Key regulators in this intestinal response seem to be the nuclear peroxisome proliferator-activated receptors alpha (PPARA) and gamma (PPARG), for which an up-regulated expression was seen in microarray and qRT-PCR data. The activation of PPARs can exert an anti-inflammatory effect with inhibition of pro-inflammatory cytokines and a decrease in cell recruitment. How the PPARs are activated during a Giardia infection still needs to be further elucidated.