|Shea Donohue, P|
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2004
Publication Date: 2/1/2005
Citation: Dawson, H., Beshah, E., Nishii, S., Solano-Aguilar, G., Morimoto, M., Zhao, A. Madden, K., Ledbetter, T., Dubey, J.P., Shea-Donohue, T., Lunney, J.K., and Urban, J. F. Jr. 2005. Localized multi-gene expression patterns support an evolving Th1/Th2-like paradigm in response to infections with Toxoplasma gondii and Ascaris suum. Infection and Immunity. 73(2):1116-1128. Interpretive Summary: Animal models of human disease are largely studied in mice because of the availability, cost, and reagents that can define both genetic and immunological characteristics of this species. However, the ability to extrapolate data from mice to man can be limited by their phylogenic differences. The pig can serve as an excellent model of human infectious and metabolic diseases because their immunology, physiology and dietary range is similar to man, and because pigs and man share many infectious agents directly or with the pig acting as a reservoir of agents that can be infectious for man. A major limitation of this model is the lack of well defined molecular and protein reagents to define immune responses in the pig. The current report describes the application of new technology in the form of the measurement of 25 gene expression products by "real-time" assays from 11 different local tissues sites in the pig against two important livestock and human infections. The gene expression results are confirmed by functional studies showing cellular and physiological changes in the lungs and intestine, respectively, that validates the outcome of the pattern of gene activation. This is an important technical advancement that represents an expandable technology that will soon be able to measure over 250 gene from pigs treated with different diets to measure the effect of nutrition on several other infectious and metabolic diseases. This technology will help both the veterinary and medical community through the analysis of important livestock diseases as well as by providing a more robust and relevant model of human disease.
Technical Abstract: Pigs represent an important model of human infectious disease because both species share common microbial, parasitic and zoonotic organisms, but there has been no systematic evaluation of cytokine gene expression in response to infectious agents in this species. In this study, pigs were inoculated with two clinically and economically important parasites, Toxoplasma gondii and Ascaris suum, and gene expression in 11 different tissues for 20 different swine Th1/Th2-related cytokines, cytokine receptors, and markers of immune activation were evaluated by real-time PCR. A generalized Th1-like pattern of gene expression was evident in pigs infected with T. gondii along with an increased anti-inflammatory response during the recovery phase of the infection. In contrast, an elevated Th2-like pattern was expressed during the period of expulsion of A. suum 4th stage larvae from the small intestine of pigs with low level Th1-like and anti-inflammatory cytokine gene expression. Prototypical immune and physiological markers of infection were observed in bronchial alveolar lavage cells, small intestinal smooth muscle and epithelial cells. This study validates a robust molecular approach for quantitative expression of an array of genes associated with immunity and inflammation at multiple tissue sites, and supports the pig as a useful model of infectious agents relevant to humans.