Gut Flora Allows Recovery of Oral Tolerance to Ovalbumin in Mice after Transient Breakdown Mediated by Cholera Toxin or Escherichia coli Heat-Labile Enterotoxin

Abstract

Oral tolerance, the antigen-specific immunologic unresponsiveness after antigen (Ag) feeding, is of physiologic importance in preventing antibody (Ab) responses to dietary proteins. This is important in the young, especially at weaning when numerous dietary Ag are encountered for the first time. Two related enterotoxins responsible for much diarrhea in the infant, cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT), have been shown to abrogate oral tolerance to an unrelated Ag fed simultaneously. The main objective of this study was to determine whether the gut flora can play a role in the CT- or LT-mediated abrogation of oral tolerance to the dietary protein ovalbumin (OVA), on a short-term and long-term basis. Conventional and germ-free mice were fed once or twice with toxin plus OVA. After two intraperitoneal immunizations with OVA, anti-OVA IgG and IgE Ab levels were measured. Because IgG and IgE Ab responses were detected, both CT and LT abrogated oral tolerance to OVA in conventional and germ-free mice. As time progressed (observations over 3 mo), whereas the specific IgG Ab response in the germ-free mice remained similar to that of the bicarbonate-fed controls, a hyporesponsive state was observed in conventional mice. The results showed that, although the gut flora did not prevent the CT- and LT-mediated abrogation of oral tolerance, it did shorten the effect and allow oral tolerance to be recovered.