Microbial Host-Interaction: Tolerance versus Allergy

64th Nestlé Nutrition Institute Workshop, Pediatric Program, Sydney, November 2008

Editor(s): Brandtzaeg P. (Oslo) 
Isolauri E. (Turku) 
Prescott S.L. (Perth, W.A.) 
Table of Contents
Vol. 64, No. , 2009
Section title: Development of Normal Tolerance
Brandtzaeg P, Isolauri E, Prescott SL (eds): Microbial–Host Interaction: Tolerance versus Allergy. Nestlé Nutr Inst Workshop Ser Pediatr Program, vol 64, pp 23–43, Nestec Ltd., Vevey/S. Karger AG, Basel, © 2009

‘ABC’ of Mucosal Immunology

Brandtzaeg P.
Laboratory for Immunohistochemistry and Immunopathology, Institute and Division of Pathology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Two adaptive homeostatic mechanisms normally preserve mucosal integrity: (i) immune exclusion mediated by secretory antibodies to inhibit penetration of potentially dangerous microorganisms and proteins, and (ii) immunosuppression to counteract hypersensitivity against innocuous antigens. The latter mechanism is called ‘oral tolerance’ when induced via the gut. Similar mechanisms are suppressive against commensal bacteria. Such two-layered anti-inflammatory defense explains why persistent allergy to dietary proteins is not more common, with the exception of gluten intolerance (celiac disease) where abrogation of mucosal homeostasis is overt. Thus, mucosally induced tolerance is generally a robust adaptive mechanism in view of the fact that a ton of food may pass annually through the gut of an adult – regularly giving rise to uptake of intact dietary antigens in the nanogram range after a meal. However, the immunoregulatory network and the epithelial barrier are poorly developed in the neonatal period, which therefore is critical with regard to priming for allergy. Notably, the postnatal development of mucosal immune homeostasis depends on appropriate microbial colonization. In this process, antigen-presenting cells are ‘decision makers’, linking innate and adaptive immunity. Their microbe-sensing function is influenced by both microbial products and dietary constituents, including vitamin A and lipids such as polyunsaturated n-3 fatty acids.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Didierlaurent A, Goulding J, Patel S, et al: Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection. J Exp Med 2008;205:323-329
  2. Barton GM, Medzhitov R: Toll-like receptor signaling pathways. Science 2003;300:1524-1525
  3. Nagler-Anderson C: Man the barrier! Strategic defences in the intestinal mucosa. Nat Rev Immunol 2001;1:59-67
  4. Brandtzaeg P: History of oral tolerance and mucosal immunity. Ann NY Acad Sci 1996;778:1-27
  5. Helgeland L, Brandtzaeg P: Development and function of intestinal B and T cells. Microbiol Ecol Health Dis 2000;12:(suppl 2)110-127
  6. Brandtzaeg P: Role of local immunity and breast-feeding in mucosal homeostasis and defence against infections. (eds) Calder PC, Field CJ, Gill HS: Nutrition and Immune Function Frontiers in Nutritional Science, Oxon, CABI International, 2002;273-320
  7. Moreau MC, Gaboriau-Routhiau V: Immunomodulation by the gut microflora and probiotics. Probiotics 2000;3:69-114
  8. Hooper LV, Wong MH, Thelin A, et al: Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001;291:881-884
  9. Neish AS, Gewirtz AT, Zeng H, et al: Prokaryotic regulation of epithelial responses by inhibition of IκB-α ubiquitination. Science 2000;289:1560-1563
  10. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al: Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 2004;118:229-2241
  11. Artis D: Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol 2008;8:411-420
  12. Rimoldi M, Chieppa M, Salucci V, et al: Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 2005;6:507-514
  13. Lotz M, Gütle D, Walther S, et al: Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. J Exp Med 2006;203:973-984
  14. Eggesbø M, Botten G, Stigum H, et al: Is delivery by cesarean section a risk factor for food allergy?. J Allergy Clin Immunol 2003;112:420-426
  15. Brandtzaeg P: Johansen F-E: Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev 2005;206:32-63
  16. Brandtzaeg P, Nilssen DE, Rognum TO, Thrane PS: Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol Clin North Am 1991;20:397-439
  17. Mora JR, von Andrian UH: Differentiation and homing of IgA-secreting cells. Mucosal Immunol 2008;1:96-109
  18. Weaver LT, Wadd N, Taylor CE, et al: The ontogeny of serum IgA in the newborn. Pediatr Allergy Immunol 1991;2:2-75
  19. Brandtzaeg P: Johansen F-E: IgA and intestinal homeostasis. (eds) Kaetzel CS: Mucosal Immune Defense: Immunoglobulin A New York, Springer Science+Business Media, 2007;221-268
  20. Kraus TA, Toy L, Chan L, et al: Failure to induce oral tolerance to a soluble protein in patients with inflammatory bowel disease. Gastroenterology 2004;126:1771-1778
  21. Brandtzaeg P: The changing immunological paradigm in coeliac disease. Immunol Lett 2006;105:127-139
  22. US Department of Health: Evidence Report/Technology Assessment Report No 153: Breastfeeding and Maternal and Infant Health Outcomes in Developed Countries. Rockville, Agency for Healthcare Research and Quality 2007;Publ No 07-E007
  23. Field CJ: The immunological components of human milk and their effect on immune development in infants. J Nutr 2005;135:1-4
  24. Verhasselt V, Milcent V, Cazareth J, et al: Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma. Nat Med 2008;14:170-175
  25. Brandtzaeg P: Mucosal immune regulation and food allergy. (eds) Koletzko S: Food Allergy in Childhood. Causes and Consequences 1Int Symp Perspectives in Pediatric Gastroenterology Fulda, 2006;Heilbronn, SPS Publications, 2007;11-51
  26. Worbs T, Bode U, Yan S, et al: Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells. J Exp Med 2006;203:519-527
  27. Guarner F, Bourdet-Sicard R, Brandtzaeg P, et al: Mechanisms of disease: the hygiene hypothesis revisited. Nat Clin Pract Gastroenterol Hepatol 2006;3:275-284
  28. von Boehmer H: Oral tolerance: is it all retinoic acid?. J Exp Med 2007;204:1737-1739
  29. Jones G: Susceptibility to asthma and eczema from mucosal and epidermal expression of distinctive genes. Curr Allergy Asthma Rep 2007;7:11-17
  30. Kalliomäki M, Salminen S, Poussa T, et al: Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003;361:1869-1871
  31. Darrasse-Jèze G, Marodon G, Salomon BL, et al: Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses. Blood 2005;105:4715-4721
  32. Holt PG, Thomas WR: Sensitization to airborne environmental allergens: unresolved issues. Nat Immunol 2005;6:957-960

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50