Abstract
Oral administration of dietary antigen (Ag) results in the systemic Ag-specific immunologic unresponsiveness termed oral tolerance. Its induction is of importance in the young where numerous symptoms are associated with IgE-mediated food-hypersensitivity reactions. Two related enterotoxins, cholera toxin and Escherichia coli heat-labile enterotoxin, have been shown to abrogate oral tolerance (i.e. IgG and IgE antibody(Ab) unresponsiveness) to an unrelated and simultaneously fed Ag. However, a critical role has been suggested for the gut flora in recovery of a hyporesponsive state. The purpose of the present study was to investigate whether the Staphylococcus aureus enterotoxin B (SEB) and Clostridium perfringens type A enterotoxin (CPE), involved in many diarrheas, could affect the induction and long-term persistence of oral tolerance to ovalbumin (OVA). Using conventional and germ-free mice fed once or twice with enterotoxin plus OVA, we investigated the possible role of the indigenous gut flora. In addition, we tested the influence of CPE synthesized in vivo in the digestive tract of gnotobiotic mice on the induction of OVA-specific oral tolerance. Mice were immunized intraperitoneally with OVA twice, and IgG and IgE Ab levels were measured by ELISA. Neither SEB nor CPE, orally given or synthesized in vivo (CPE), prevented the induction of oral tolerance to OVA. Moreover, the IgG Ab unresponsiveness persisted over 2 mo in the conventional mice fed with toxin plus OVA as also observed in the OVA controls. The results indicate that, independent of the gut flora's influence, SEB and CPE did not affect the induction and long-term persistence of oral tolerance to co-ingested Ag.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- Ag:
-
antigen
- Ab:
-
antibody
- SEB:
-
Staphylococcus aureus enterotoxin B
- CPE:
-
Clostridium perfringens type A enterotoxin
- CT:
-
cholera toxin
- LT:
-
Escherichia coli heat-labile enterotoxin
- OVA:
-
ovalbumin
- Bic:
-
bicarbonate solution
- HRP:
-
horseradish peroxidase
References
Mowat AM 1987 The regulation of immune responses to dietary protein antigens. Immunol Today 8: 93–98.
Friedman A, Al-Sabbagh A, Santos LMB, Fishman-Lobell J, Polanski M, Prabhu Das M, Khoury SJ, Weiner HL 1994 Oral tolerance: a biologically relevant pathway to generate peripheral tolerance against external and self antigens. Chem Immunol 58: 259–290.
Sampson HA, Burks AW 1996 Mechanisms of food allergy. Annu Rev Nutr 16: 161–177.
Rolfe RD 1990 Sequential development of the human intestinal microbial flora. In: Old Herborn University Seminar Monograph 1. Microbial Ecology of the Human Digestive Tract. Herborn-Dill, Germany, 48–60.
Van der Waaij D, Van der Waaij BD 1990 The colonization resistance of the digestive tract in different animal species and in man; a comparative study. Epidemiol Infect 105: 237–243.
Grady GF, Keusch GT 1971 Pathogenesis of bacterial diarrheas. N Engl J Med 285: 831–841.
Sack RB 1980 Enterotoxigenic Escherichia coli: identification and characterization. J Infect Dis 142: 279–286.
Elson CO, Ealding W 1984 Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen. J Immunol 133: 2892–2897.
Clements JD, Hartzog NM, Lyon FL 1988 Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens. Vaccine 6: 269–277.
Pierre P, Denis O, Bazin H, Mbongolo Mbella E, Vaerman JP 1992 Modulation of oral tolerance to ovalbumin by cholera toxin and its B subunit. Eur J Immunol 22: 3179–3182.
Gaboriau-Routhiau V, Moreau MC 1996 Gut flora allows recovery of oral tolerance to ovalbumin in mice after transient breakdown mediated by cholera toxin or Escherichia coli heat-labile enterotoxin. Pediatr Res 39: 625–629.
Spero L, Johnson-Winegar A, Schmidt JJ 1988 Enterotoxins of staphylococci. In: Hardegree MC, Tu AT (eds) Bacterial Toxins. Handbook of Natural Toxins. Marcel Dekker, New York, pp 132–163.
McClane BA 1992 Clostridium perfringens enterotoxin: structure, action and detection. J Food Safety 12: 237–252.
Sacquet E, Raibaud P, Garnier J 1971 . Etude comparée de la microflore de l'estomac, de l'intestin grêle et du caecum de rat “holoxénique” (conventionnel), et de ses modifications à la suite de diverses interventions chirugicales: anse aveugle, déviations biliaires. Ann Inst Pasteur 120: 501–524.
Popoff MR 1984 Clostridium perfringens type A enterotoxin: a rapid method for preparation of a specific antiserum using an enterotoxin purified by the polyacrylamide gel electrophoresis technique. FEMS Microbiol Lett 21: 1–5.
Raibaud P, Dickinson AB, Sacquet E, Charlier H, Mocquot G 1966 La microflore du tube digestif du rat. I. Techniques d'étude et milieux de culture proposés. Ann Inst Pasteur 110: 568–590.
Skjelkvale R, Uemura T 1977 Experimental diarrhoea in human volunteers following oral administration of Clostridium perfringens enterotoxin. J Appl Bacteriol 43: 281–286.
Raibaud P 1991 Bacterial interactions in the gut. In: Fuller R (ed) Probiotics Chapman & Hall, New York, pp 9–28.
Strobel S, Ferguson A 1987 Persistence of oral tolerance in mice fed ovalbumin is different for humoral and cell-mediated immune responses. Immunology 60: 317–318.
Moreau MC, Corthier G 1988 Effect of the gastrointestinal microflora on induction and maintenance of oral tolerance to ovalbumin in C3H/HeJ mice. Infect Immun 56: 2766–2768.
Moreau MC, Gaboriau-Routhiau V 1996 The absence of gut flora, the doses of antigen ingested and aging affect the long-term peripheral tolerance induced by ovalbumin feeding in mice. Res Immunol 147: 49–59.
McDonel JL 1979 The molecular mode of action of Clostridium perfringens enterotoxin. Am J Clin Nutr 32: 210–218.
McClane BA, Wnek AP 1990 Studies of Clostridium perfringens enterotoxin action at different temperatures demonstrate a correlation between complex formation and cytotoxicity. Infect Immun 58: 3109–3115.
Lionetti P, Spencer J, Breese EJ, Murch SH, Taylor J, MacDonald TT 1993 Activation of mucosal Vβ3+ T cells and tissue damage in human small intestine by the bacterial superantigen,Staphylococcus aureus enterotoxin B. Eur J Immunol 23: 664–668.
Spangler BD 1992 Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol Rev 56: 622–647.
Snider DP 1995 The mucosal adjuvant activities of ADP-ribosylating bacterial enterotoxins. Crit Rev Immunol 15: 317–348.
Migita K, Ochi A 1994 Induction of clonal anergy by oral administration of staphylococcal enterotoxin B. Eur J Immunol 24: 2081–2086.
Marrack P, Kappler J 1990 The staphylococcal enterotoxins and their relatives. Science 248: 705–711.
Acknowledgements
The authors thank C. Dubuquoy for technical assistance, G. Corthier, M. Coste, M. Dubarry, and M. R. Popoff for helpful assistance in purifying and assaying the C. perfringens enterotoxin, and G. Milon for critical reading of the manuscript.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gaboriau-Routhiau, V., Moreau, MC. Oral Tolerance to Ovalbumin in Mice: Induction and Long-Term Persistence Unaffected by Staphylococcus aureus Enterotoxin B and Clostridium perfringens Type A Enterotoxin. Pediatr Res 42, 503–508 (1997). https://doi.org/10.1203/00006450-199710000-00014
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199710000-00014
