E-038. Anti-Toxin Serum IgG Antibodies Protect the Intestinal Epithelium of Mice from the Effects of the Shiga-Like Toxin Ricin
The shiga-like family of ribosome inactivating proteins (RIPs), including shiga toxin and ricin, are increasingly a threat to public health, because of their association with emerging food- and water-borne infections and their potential use as bioterrorism agents. We have developed a mouse model of intestinal ricin intoxication to better understand the effects of shiga-like toxins on intestinal epithelial cells in vivo, and to determine the contributions of secretory IgA (SIgA) and serum IgG in protecting the epithelium from toxin-induced damage. Mice challenged intragastrically with ricin demonstrated widespread villous atrophy, inter-epithelial swelling, separation of the epithelial cells from the basal lamina, and sloughing of enterocytes from the tips of villi. Coincident with epithelial damage was a localized increase in monocyte chemotactic protein-1 (MCP-1), suggesting that inflammation may contribute to disease severity. Immunity to intestinal ricin intoxication was achieved by immunizing mice intragastrically with ricin toxoid (RT), and correlated with elevated levels of anti-toxin fecal IgA and serum IgG antibodies. RT-vaccinated, polymeric immunoglobulin receptor (pIgR) deficient mice lacked detectable levels of anti-toxin SIgA, yet were immune to the effects of intragastric toxin challenge, suggesting a role for serum IgG in protecting intestinal epithelial cells from ricin. Using the so-called mouse ‘backpack’ tumor model, as well as passive transfer studies, we provide evidence that in fact anti-toxin IgG monoclonal antibodies are capable of mediating both systemic and mucosal immunity to ricin. These results raise fundamental questions about how IgG functions in the intestinal mucosal, and highlights the prospect of developing parenteral-based vaccines and therapies capable of conferring immunity to ricin irrespective of the route of exposure. This work is supported by grants from the Northeast Biodefense Center and the NIAID.
135/E. Dendritic Cells and Immune Responses to Microbes
Tuesday, 10:30 am | Poster Hall