Plant & Animal Genomes XIV Conference

January 14-18, 2006
Town & Country Convention Center
San Diego, CA

Molecular Mechanisms Of Cholera Toxin-Induced Mucosal Immunity In The Porcine Gut

Cheryl M.T. Dvorak , David R. Brown , Michael P. Murtaugh

  Department of Veterinary and Biomedical Science, University of Minnesota, 1971 Commonwealth Ave, St. Paul, MN 55108

The molecular mechanisms regulating host/pathogen interactions involved in infectious disease resistance in livestock species is not well known. Development of immune-mediated protection methods is hindered by a lack of understanding of the biology of host resistance in intestinal tissues. Cholera toxin (CT) has the rare ability for a protein of inducing robust mucosal immunity in the gut. It is therefore an excellent model with which to determine mechanisms of adjuvanticity and immunogenicity at intestinal mucosal surfaces. Using an ex vivo Ussing chamber model, intestinal tissues were treated with CT and the immediate immune response was examined. In the luminal bathing media, IL-6 was not altered, IL-1beta and IL-8 were increased 2 fold, and IL-10 was increased 5 fold following CT treatment. Levels of IL-8 were quite high, while IL-1beta levels were low. Changes in gene expression of various cytokines and chemokines were identified after CT treatment of gut tissues. A comparison of jejunal and ileal Peyer’s patch and absorptive tissues was also performed to determine which tissues act as the inductive site of the immune response to CT. These data suggest that the potent mucosal adjuvanticity and immunogenicity of CT may derive from rapid alterations in gene expression, especially of inflammatory cytokines, at the site of first antigen encounter with the immune system. The characterization of these early events in immune induction may elucidate potential biological mechanisms for mucosal immune induction in the enteric system leading to the development of effective vaccines against enteric pathogens.