GastricHelicobacterInfection Inhibits Development of Oral Tolerance to Food Antigens in Mice

Abstract

The increase in the transcellular passage of intact antigens across the digestive epithelium infected with Helicobacter pylori may interfere with the regulation of mucosal immune responses. The aim of this work was to study the capacity of Helicobacter infection to inhibit the development of oral tolerance or to promote allergic sensitization and the capacity of a gastro-protective agent, rebamipide, to interfere with these processes in mice. Oral tolerance to ovalbumin (OVA) was studied in 48 C3H/He 4-week-old mice divided into four groups: (i) OVA-sensitized mice; (ii) OVA-"tolerized" mice (that is, mice that were rendered immunologically tolerant); (iii) H. felis-infected, OVA-tolerized mice; (iv) and H. felis-infected, OVA-tolerized, rebamipide-treated mice. Oral sensitization to hen egg lysozyme (HEL) was studied in 48 mice divided into four groups: (i) controls; (ii) HEL-sensitized mice; (iii) H. felis-infected, HEL-sensitized mice; and (iv) H. felis-infected, HEL-sensitized, rebamipide-treated mice. Specific anti-OVA or anti-HEL immunoglobulin E (IgE) and IgG1/IgG2a serum titers were measured by enzyme-linked immunosorbent assay. Additionally, the capacity of rebamipide to interfere with antigen presentation and T-cell activation in vitro, as well as absorption of rebamipide across the epithelial monolayer, was tested. H. felis infection led to the inhibition of oral tolerance to OVA, but rebamipide prevented this inhibitive effect of H. felis. H. felis infection did not enhance the sensitization to HEL, but rebamipide inhibited the development of this sensitization. Moreover, rebamipide inhibited in a dose-dependent manner antigen presentation and T-cell activation in vitro and was shown to be able to cross the epithelium at a concentration capable of inducing this inhibitory effect. We conclude that H. felis can inhibit the development of oral tolerance to OVA in mice and that this inhibition is prevented by rebamipide.

Effect of Rebamipide on the Colonic Barrier in Interleukin-10-Deficient Mice

“…The beneficial effect of rebamipide with respect to the epithelial barrier, already recognized for gastric and small intestinal mucosa [7,17], has now been shown for colonic mucosa. This effect concerns both paracellular and transcellular permeability.…”

Gastrointestinal Candida colonisation promotes sensitisation against food antigens by affecting the mucosal barrier in mice

“…45 The authors also reported that Helicobacter infection inhibits the development of oral tolerance by preventing anti-OVA IgE suppression, normally induced after OVA feeding. 49 Oral tolerance is characterised by induction of a state of systemic immune non-responsiveness towards antigens present in the gastrointestinal tract. [50][51][52] This mechanism presumably prevents the development of food allergy.…”

Helicobacter pylori Activates Myosin Light-Chain Kinase To Disrupt Claudin-4 and Claudin-5 and Increase Epithelial Permeability

“…However, whereas these pathogens generally cause a self-limiting diarrheal disease, H. pylori chronically infects the human stomach. Recent studies have shown that H. pylori may allow the transepithelial entry of food antigens, and the infection has been associated with the development of food allergies in some patients (8,15,33,34). Future research will determine if strain-specific gastric barrier disruptions may explain, at least in part, the variable clinical outcomes seen in response to H. pylori infection.…”

“…Yet, while the host inflammatory response may contribute to an increase in permeability in human subjects (19,38), the ability of the bacterium to directly disrupt tight junctions of the human gastric epithelium remains controversial (2,44). Recent findings showed that H. pylori has the ability to increase the passage of food antigens across human gastric biopsies (33), as well as in animal model systems (34). These observations are consistent with observations that the infection may be associated with the development of food allergy (8,15).…”