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How dietary antigens access the mucosal immune system

Published online by Cambridge University Press:  28 February 2007

M. Heyman
M. Heyman*
Affiliation:
INSERM E9925, Faculté Necker, 156 rue de Vaugirard, 75730 Paris, France
*
Corresponding Author: Dr M. Heyman, fax +33 1 40 61 56 38, email heyman@necker.fr
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Abstract

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The intestinal epithelium is a selective barrier where incompletely-digested food antigens are transmitted to the immune system. Food antigens are often the starting point of intestinal diseases such as food allergy or coeliac disease. The intestinal epithelial cells (IEC) take up and process food antigens mainly by fluid-phase transcytosis involving two functional pathways, one minor direct pathway without degradation and another major lysosomal degradative pathway. Among the peptidic metabolites generated during transepithelial transport of luminal antigens, some have a molecular mass compatible with a binding to restriction (major histocompatibility complex; MHC) molecules; the latter can be up regulated on enterocytes, especially in inflammatory conditions. Indeed, interferon-γ not only increases the paracellular absorption of antigens, but also their transcytosis across epithelial cells. It has been reported that enterocytes may even directly present peptidic epitopes to underlying T-cells. As a new potential way of transmitting peptidic information to the local or systemic immune system, the secretion by IEC of antigen-presenting vesicles called exosomes and bearing MHC–peptide complexes has recently been proposed. Many other factors such as nutritional or environmental factors can also influence the properties of the epithelial barrier and the outcome of the immune response to lumen antigens.

Keywords

Intestinal absorptionFood antigensFood allergyEpithelial barrierMucosal immunity
Type
Symposium on ‘Dietary influences on mucosal immunity’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 4 , November 2001 , pp. 417 - 426
Copyright
Copyright © The Nutrition Society 2001

References

Astwood, JD, Leach, JN & Fuchs, RL (1998) Stability of food allergens to digestion in vitro. Nature Biotechnology 14, 1269–1273.CrossRefGoogle Scholar
Axelsson, I, Jakobsson, I, Lindberg, T, Polberger, S, Benediktsson, B & Raiha, N (1989) Macromolecular absorption in preterm and term infants. Acta Paediatrica Scandinavica 78, 532–537.CrossRefGoogle ScholarPubMed
Bland, PW & Warren, LG (1986) Antigen presentation by epithelial cells of the rat small intestine. I. Kinetics, antigen specificity and blocking by anti-Ia antisera. Immunology 58, 1–7.Google ScholarPubMed
Brandtzaeg, P, Halstensen, TS, Huitfeldt, HS, Krajci, P, Kvale, D, Scott, H & Thrane, PS (1992) Epithelial expression of HLA, secretory component (poly-Ig receptor), and adhesion molecules in the human alimentary tract. Annals of the New York Academy of Sciences 664, 157–179.CrossRefGoogle ScholarPubMed
Bruce, MG & Ferguson, A (1986) Oral tolerance to ovalbumin in mice: studies of chemically modified and ‘biologically filtered’ antigen. Immunology 57, 627–630.Google ScholarPubMed
Cornell, R, Walker, WA & Isselbacher, KJ (1971) Small intestinal absorption of horseradish peroxidase. A cytochemical study. Laboratory Investigation 25, 42–48.Google ScholarPubMed
Corrado, G, Luzzi, I, Lucarelli, S, Frediani, T, Pacchiarotti, C, Cavaliere, M, Rea, P & Cardi, E (1998) Positive association between. Helicobacter pylori infection and food allergy in children. Scandinavian Journal of Gastroenterology 33, 1135–1139.Google ScholarPubMed
Curtis, GH & Gall, DG (1992) Macromolecular transport by rat gastric mucosa. American Journal of Physiology 262, G1033–G1040.Google ScholarPubMed
Denzer, K, Kleijmeer, MJ, Heijnen, HF, Stoorvogel, W & Geuze, HJ (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. Journal of Cell Science 113, 3365–3374.CrossRefGoogle ScholarPubMed
Ducroc, R, Heyman, M, Beaufrere, B, Morgat, JL & Desjeux, JF (1983) Horseradish peroxidase transport across rabbit jejunum and Peyer's patches in vitro. American Journal of Physiology 245, G54–G58.Google ScholarPubMed
Figura, N, Perrone, A, Gennari, C, Orlandini, G, Bianciardi, L, Giannace, R, Vaira, D, Vagliasinti, M & Rottoli, P (1999) Food allergy and Helicobacter pylori infection. Italian Journal of Gastroenterology and Hepatology 31, 186–191.Google ScholarPubMed
Furrie, E, Turner, MW & Strobel, S (1995) Partial characterization of a circulating tolerogenic moiety which, after a feed of ovalbumin, suppresses delayed-type hypersensitivity in recipient mice. Immunology 86, 480–486.Google ScholarPubMed
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. Pediatric Research 39, 625–629.CrossRefGoogle ScholarPubMed
Gonnella, PA, Chen, Y, Inobe, J, Komagata, Y, Quartulli, M & Weiner, HL (1998) In situ immune response in gut-associated lymphoid tissue (GALT) following oral antigen in TCR-transgenic mice. Journal of Immunology 160, 4708–4718.CrossRefGoogle ScholarPubMed
Gupta, P, Andrew, H, Kirschner, BS & Guandalini, S (2000) Is lactobacillus GG helpful in children with Crohn's disease? Results of a preliminary, open-label study. Journal of Pediatric Gastroenterology and Nutrition 31, 453–457.Google ScholarPubMed
Hershberg, RM, Cho, DH, Youakim, A, Bradley, MB, Lee, JS, Framson, PE & Nepom, GT (1998) Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells. Journal of Clinical Investigation 102, 792–803.CrossRefGoogle ScholarPubMed
Hershberg, RM, Framson, PE, Cho, DH, Lee, LY, Kovats, S, Beitz, J, Blum, JS & Nepom, GT (1997) Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing. Journal of Clinical Investigation 100, 204–215.CrossRefGoogle ScholarPubMed
Heyman, M, Corthier, G, Lucas, F, Meslin, JC & Desjeux, JF (1989 a) Evolution of the caecal epithelial barrier during. Clostridium difficile infection in the mouse. Gut 30, 1087–1093.CrossRefGoogle ScholarPubMed
Heyman, M, Corthier, G, Petit, A, Meslin, JC, Moreau, C & Desjeux, JF (1987) Intestinal absorption of macromolecules during viral enteritis: an experimental study on rotavirus-infected conventional and germ-free mice. Pediatric Research 22, 72–78.CrossRefGoogle Scholar
Heyman, M, Crain-Denoyelle, AM, Corthier, G, Morgat, JL & Desjeux, JF (1986) Postnatal development of protein absorption in conventional and germ-free mice. American Journal of Physiology 251, G326–G331.Google ScholarPubMed
Heyman, M, Crain-Denoyelle, AM & Desjeux, JF (1989 b) Endocytosis and processing of protein by isolated villus and crypt cells of the mouse small intestine. Journal of Pediatric Gastroenterology and Nutrition 9, 238–245.Google ScholarPubMed
Heyman, M, Darmon, N, Dupont, C, Dugas, B, Hirribaren, A, Blaton, MA & Desjeux, JF (1994) Mononuclear cells from infants allergic to cow's milk secrete tumor necrosis factor alpha, altering intestinal function. Gastroenterology 106, 1514–1523.CrossRefGoogle ScholarPubMed
Heyman, M & Desjeux, J (1996) Antigen handling by intestinal epithelial cells. In Antigen Presentation by Intestinal Epithelial Cells, pp. 1–16 [Kaiserlian, D, editor]. Heidelberg: Springer–Verlag.Google Scholar
Heyman, M, Ducroc, R, Desjeux, JF & Morgat, JL (1982) Horseradish peroxidase transport across adult rabbit jejunum in vitro. American Journal of Physiology 242, G558–G564.Google ScholarPubMed
Heyman, M, Grasset, E, Ducroc, R & Desjeux, JF (1988) Antigen absorption by the jejunal epithelium of children with cow's milk allergy. Pediatric Research 24, 197–202.CrossRefGoogle ScholarPubMed
Host, A (1997) Cow's milk allergy. Journal of the Royal Society of Medicine 90, Suppl. 30, 34–39.CrossRefGoogle ScholarPubMed
Isolauri, E, Majamaa, H, Arvola, T, Rantala, I, Virtanen, E & Arvilommi, H (1993) Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats. Gastroenterology 105, 1643–1650.CrossRefGoogle ScholarPubMed
Kaiserlian, D, Vidal, K & Revillard, JP (1989) Murine enterocytes can present soluble antigen to specific class II-restricted CD4+ T cells. European Journal of Immunology 19, 1513–1516.CrossRefGoogle ScholarPubMed
Kapel, N, Matarazzo, P, Haouchine, D, Abiola, N, Guerin, S, Magne, D, Gobert, JG & Dupont, C (1999) Fecal tumor necrosis factor alpha, eosinophil cationic protein and IgE Levels in infants with cow's milk allergy and gastrointestinal manifestations. Clinical Chemistry and Laboratory Medicine 37, 29–32.CrossRefGoogle ScholarPubMed
Madara, JL (1990) Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium: physiological rearrangement of tight junctions. Journal of Membrane Biology 116, 177–184.CrossRefGoogle ScholarPubMed
Madara, JL & Stafford, J (1989) Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. Journal of Clinical Investigation 83, 724–727.CrossRefGoogle ScholarPubMed
Mahé, S, Messing, B, Thuillier, F & Tomé, D (1991) Digestion of bovine milk proteins in patients with a high jejunostomy. American Journal of Clinical Nutrition 54, 534–538.CrossRefGoogle ScholarPubMed
Majamaa, H, Miettinen, A, Laine, S & Isolauri, E (1996) Intestinal inflammation in children with atopic eczema: faecal eosinophil cationic protein and tumour necrosis factor-alpha as non-invasive indicators of food allergy. Clinical and Experimental Allergy 26, 181–187.CrossRefGoogle ScholarPubMed
Marcon-Genty, D, Tome, D, Dumontier, AM, Kheroua, O & Desjeux, JF (1989) Permeability of milk protein antigens across the intestinal epithelium in vitro. Reproduction Nutrition Developpement 29, 717–723.CrossRefGoogle ScholarPubMed
Matysiak-Budnik, T, Terpend, K, Alain, S, Sanson le Pors, MJ, Desjeux, JF, Megraud, F & Heyman, M (1998) Helicobacter pylori alters exogenous antigen absorption and processing in a digestive tract epithelial cell line model. Infection and Immunity 66, 5785–5791.CrossRefGoogle Scholar
Mayer, L & Shlien, R (1987) Evidence for function of Ia molecules on gut epithelial cells in man. Journal of Experimental Medicine 166, 1471–1483.CrossRefGoogle ScholarPubMed
Moreau, MC & Corthier, G (1988) Effect of the gastrointestinal microflora on induction and maintenance of oral tolerance to ovalbumin in C3H/HeJ mice. Infection and Immunity 56, 2766–2768.CrossRefGoogle ScholarPubMed
Neish, AS, Gewirtz, AT, Zeng, H, Young, AN, Hobert, ME, Karmali, V, Rao, AS & Madara, JL (2000) Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination. Science 289, 1560–1563.CrossRefGoogle ScholarPubMed
Philpott, DJ, McKay, DM, Mak, W, Perdue, MH & Sherman, PM (1998) Signal transduction pathways involved in enterohemorrhagic. Escherichia coli-induced alterations in T84 epithelial permeability. Infection and Immunity 66, 1680–1687.CrossRefGoogle ScholarPubMed
Rodriguez, P, Heyman, M, Candalh, C, Blaton, MA & Bouchaud, C (1995) Tumour necrosis factor-alpha induces morphological and functional alterations of intestinal HT29 cl. 19A cell monolayers. Cytokine 7, 441–448.CrossRefGoogle ScholarPubMed
Saidi, D, Heyman, M, Kheroua, O, Boudraa, G, Bylsma, P, Kerroucha, R, Chekroun, A, Maragi, JA, Touhami, M & Desjeux, JF (1995) Jejunal response to beta-lactoglobulin in infants with cow's milk allergy. Comptes Rendus Academie des Sciences Paris Serie 3. 318, 683–689.Google ScholarPubMed
Soloway, P, Fish, S, Passmore, H, Gefter, M, Coffee, R & Manser, T (1991) Regulation of the immune response to peptide antigens: differential induction of immediate-type hypersensitivity and T cell proliferation due to changes in either peptide structure or major histocompatibility complex haplotype. Journal of Experimental Medicine 174, 847–858.CrossRefGoogle ScholarPubMed
Terpend, K, Blaton, MA, Candalh, C, Wal, JM, Pochart, P & Heyman, M (1999) Intestinal barrier function and cow's milk sensitization in guinea pigs fed milk or fermented milk. Journal of Pediatric Gastroenterology and Nutrition 28, 191–198.CrossRefGoogle ScholarPubMed
Terpend, K, Boisgerault, F, Blaton, MA, Desjeux, JF & Heyman, M (1998) Protein transport and processing by human HT29–19A intestinal cells: effect of interferon gamma. Gut 42, 538–545.CrossRefGoogle ScholarPubMed
Van Niel, G, Raposo, G, Hershberg, R, Boussac, M, Cerf-Bensussan, N & Heyman, M (2001) Secretion of antigen presenting vesicles (exosomes) by intestinal epithelial cells: phenotypic characterization. Gastroenterology 121 (In the Press).CrossRefGoogle Scholar
Wheeler, EE, Challacombe, DN, Kerry, PJ & Pearson, EC (1993) A morphological study of beta-lactoglobulin absorption by cultured explants of the human duodenal mucosa using immunocytochemical and cytochemical techniques. Journal of Pediatric Gastroententerology and Nutrition 16, 157–164.Google ScholarPubMed
Williamson, E, Westrich, GM & Viney, JL (1999) Modulating dendritic cells to optimize mucosal immunization protocols. Journal of Immunology 163, 3668–3675.CrossRefGoogle ScholarPubMed
Yang, PC, Berin, MC, Yu, LC, Conrad, DH & Perdue, MH (2000) Enhanced intestinal transepithelial antigen transport in allergic rats is mediated by IgE and CD23 (FcepsilonRII). Journal of Clinical Investigation 106, 879–886.CrossRefGoogle Scholar