Protection of the intestinal epithelium from the direct effects of a shiga‐like enterotoxin is conferred by anti‐toxin serum IgG

Abstract

Shiga‐like enterotoxins are extremely potent ribosome inactivating proteins (RIPs) associated with emerging foodborne E.coli infections and, in the case of ricin, are considered potential bioterrorism agents. A hallmark of this family of toxins is their ability to act directly on mature absorptive enterocytes, inducing epithelial cell sloughing and triggering pro‐inflammatory signaling cascades. We have developed a mouse model of intestinal ricin intoxication to better understand the effects of shiga‐like toxins on epithelial physiology and barrier function in vivo, and to determine the role of secretory IgA and serum IgG in protecting the epithelium from toxin‐induced damage. Preliminary studies using available chemokine and chemokine receptor knock‐out mice suggest ricin‐induced epithelial damage is the result of both direct cytotoxic effects and bystander inflammatory responses, possibly emanating from lamina propria leukocytes. We also report that anti‐toxin secretory IgA and serum IgG antibodies, elicited by vaccination or administered passively, are sufficient to protect the intestinal epithelium from ricin intoxication. We are currently investigating, both in vitro and in vivo, the mechanistic interplay between inflammation, epithelial barrier function and serum IgG‐mediated intestinal immunity. This work is supported by the NIH and the Northeast Biodefense Center.