Advertisement

Protection of Mucosal Epithelia by IgA: Intracellular Neutralization and Excretion of Antigens

  • Michael E. Lamm

Mucosal immunoglobulin A (IgA) antibodies are synthesized by local plasma cells in the lamina propria and are largely destined for export through the lining epithelium into the luminal secretions. Here, IgA antibodies can bind antigens and exclude them from the body, as has long been appreciated. It is becoming increasingly apparent, though, that passage through mucosal epithelium creates additional opportunities for IgA antibodies to function in host defense. For example, IgA antibodies against viruses can directly counter infections within mucosal epithelium, and immune complexes formed in the lamina propria containing locally produced IgA antibodies can pass through the epithelium via the same route and mechanism as free IgA. Thus, IgA antibodies might first encounter antigens in three anatomic compartments in relation to mucosal epithelium: in the lumen, in the epithelium itself, or in the lamina propria (Lamm, 1997). The nonclassical defense functions of IgA, in which IgA antibodies initially bind antigens in the lamina propria or inside the lining epithelial cells, are the focus of this chapter.

Keywords

Lamina Propria Mucosal Epithelium Secretory Component Mucosal Lamina Propria Human Intestinal Epithelial Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bomsel, M., Heyman, M., Hocini, H., Lagaye, S., Belec, L., Dupont, C., and Desgranges, C. (1998). Intracellular neutralization of HIV transcytosis across tight epithelial barriers by anti-HIV envelope protein dIgA or IgM. Immunity 9:277–287.CrossRefPubMedGoogle Scholar
  2. Bruno, M. E. C., and Kaetzel, C.S. (2005). Long-term exposure of the HT-29 human intestinal epithelial cell line to TNF causes sustained up-regulation of the polymeric Ig receptor and proinflammatory genes through transcriptional and posttranscriptional mechanisms. J. Immunol. 174:7278–7284.PubMedGoogle Scholar
  3. Burns, J. W., Siadat-Pajouh, M., Krishnaney, A. A., and Greenberg, H. B. (1996). Protective effect of rotavirus VP6-specific IgA monoclonal antibodies that lack neutralizing activity. Science 272:104–107.CrossRefPubMedGoogle Scholar
  4. Corthésy, B., Benureau, Y., Perrier, C., Fourgeux, C., Parez, N., Greenberg, H., and Schwartz-Cornil, I. (2006). Rotavirus anti-VP6 secretory immunoglobulin A contributes to protection via intracellular neutralization but not via immune exclusion. J Virol. 80:10692–10699.CrossRefPubMedGoogle Scholar
  5. Emancipator, S. N., Mestecky, J., and Lamm, M. E. (2005). IgA nephropathy and related diseases. In: Mestecky J., Bienenstock, J., Lamm, M. E., Mayer, L., McGhee, J. R., and Strober, W. (eds.), Mucosal Immunology, 3rd ed. Elsevier, San Diego, pp. 1580–1600.Google Scholar
  6. Feng, N., Lawton, J. A., Gilbert, J., Kuklin, N., Vo, P., Venkataram Prasad, B. V., and Greenberg, H. B. (2002). Inhibition of rotavirus replication by a non-neutralizing, rotavirus VP6-specific IgA mAb. J. Clin. Invest. 109:1203–1213.PubMedGoogle Scholar
  7. Fernandez, M. I., Pedron, T., Tournebize, R., Olivo-Marin, J.-C., Sansonetti, P. J., and Phalipon, A. (2003). Anti-inflammatory role for intracellular dimeric immunoglobulin A by neutralization of lipopolysaccharide in epithelial cells. Immunity 18:739–749.CrossRefPubMedGoogle Scholar
  8. Fujioka, H. S., Emancipator, S. N., Aikawa, M., Huang, D. S., Blatnik, F., Karban, T., DeFife, K., and Mazanec, M. B. (1998). Immunocytochemical colocalization of specific immunoglobulin A with sendai virus protein in infected polarized epithelium. J. Exp. Med. 188:1223–1229.CrossRefPubMedGoogle Scholar
  9. Gan, Y. J., Chodosh, J., Morgan, A., and Sixbey, J. W. (1997). Epithelial cell polarization is a determinant in the infectious outcome of immunoglobulin A-mediated entry by Epstein-Barr virus. J. Virol. 71:519–526.PubMedGoogle Scholar
  10. Harmatz, P. R., Kleinman, R. E., Bunnel, B. W., Block, K. J., and Walker, W. A. (1982). Hepatobiliary clearance of IgA immune complexes formed in the circulation. Hepatology 2:328–333.PubMedCrossRefGoogle Scholar
  11. Hayashi, M., Takenouchi, N., Asano, M., Kato, M., Tsurumachi, T., Sait, T., and Moro, I. (1997). The polymeric immunoglobulin receptor (secretory component) in a human intestinal epithelial cell line is up-regulated by interleukin-1. Immunology 92:220–225.CrossRefPubMedGoogle Scholar
  12. Hirunsatit, R., Kongruttanachok, N., Shotelersuk, K., Supiyaphun, P., Voravud, N., Sakuntabhai, A., and Mutirangura, A. (2003). Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer. BMC Genet. 4:3.CrossRefPubMedGoogle Scholar
  13. Huang, Y. T., Wright, A., Gao, X., Kulick, L., Yan, H., and Lamm, M. E. (2005). Intraepithelial cell neutralization of HIV-1 replication by IgA. J. Immunol. 174:4828–4835.PubMedGoogle Scholar
  14. Johansen, F. E., and Brandtzaeg, P. (2004). Transcriptional regulation of the mucosal IgA system. Trends Immunol. 25:150–157.CrossRefPubMedGoogle Scholar
  15. Kaetzel, C. S., Robinson, J. K., Chintalacharuvu, K. R., Vaerman, J.-P., and Lamm, M. E. (1991). The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: A local defense function for IgA. Proc. Natl. Acad. Sci. USA 88:8796–8800.CrossRefPubMedGoogle Scholar
  16. Kaetzel, C. S., Robinson, J. K., and Lamm, M. E. (1994). Epithelial transcytosis of monomeric IgA and IgG cross-linked through antigen to polymeric IgA. A role for monomeric antibodies in the mucosal immune system. J. Immunol. 152:72–76.PubMedGoogle Scholar
  17. Kvale, D., Brandtzaeg, P., and Lovhaug, D. (1988). Up-regulation of the expression of secretory component and HLA molecules in a human colonic cell line by tumour necrosis factor-l and -interferon. Scand. J. Immunol. 28:351–357.CrossRefPubMedGoogle Scholar
  18. Lamm, M. E. (1997). Interaction of antigens and antibodies at mucosal surfaces. Annu. Rev. Microbiol. 51:311–340.CrossRefPubMedGoogle Scholar
  19. Mazanec, M. B., Coudret, C. L., and Fletcher, D.R. (1995). Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies. J. Virol. 69:1339–1343.PubMedGoogle Scholar
  20. Mazanec, M. B., Kaetzel, C. S., Lamm, M. E., Fletcher, D., and Nedrud, J. G. (1992). Intracellular neutralization of virus by immunoglobulin A antibodies. Proc. Natl. Acad. Sci. USA 89:6901–6905.CrossRefPubMedGoogle Scholar
  21. Mostov, K. E., and Deitcher, D. L. (1986). Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgA. Cell 15:613–621.CrossRefGoogle Scholar
  22. Nilsen, E. M., Johansen, F. E., Kvale, D., Krajci, P., and Brandtzaeg, P. (1999). Different regulatory pathways employed in cytokine-enhanced expression of secretory component and epithelial HLA class I genes. Eur. J. Immunol. 29:168–179.CrossRefPubMedGoogle Scholar
  23. Obara, W., Iida, A., Suzuki, Y., Tanaka, T., Akiyama, F., Maeda, S., Ohnishi, Y., Yamada, R., Tsunoda, T., Takei, T., Ito, K., Honda, K., Uchida, K., Tsuchiya, K., Yumura, W., Ujiie, T., Nagane, Y., Nitta, K., Miyano, S., Narita, I., Gejyo, F., Nihei, H., Fujioka, T., and Nakamura, Y. (2003). Association of single-nucleotide polymorphisms in the polymeric immunoglobulin receptor gene with immunoglobulin A nephropathy (IgAN) in Japanese patients. J. Hum. Genet. 48:293–299.PubMedGoogle Scholar
  24. Peppard, J., Orlans, E., Payne, A. W. R., and Andrew, E. (1981). The elimination of circulating complexes containing polymeric IgA by excretion in the bile. Immunology 42:83–89.PubMedGoogle Scholar
  25. Phillips, J. O., Everson, M. P., Moldoveanu, Z., Lue, C., and Mestecky, J. (1990). Synergistic effect of IL-4 and IFN-L on the expression of polymeric Ig receptor (secretory component) and IgA binding by human epithelial cells. J. Immunol. 145:1740–1744.PubMedGoogle Scholar
  26. Piskurich, J. F., Youngman, K. R., Phillips, K. M., Hempen, P. M., Blanchard, M. H., France, J. A., and Kaetzel, C. S. (1997). Transcriptional regulation of the human polymeric immunoglobulin receptor gene by interferon-t. Mol. Immunol. 34:75–91.CrossRefPubMedGoogle Scholar
  27. Robinson, J. K., Blanchard, T. G., Levine, A. D., Emancipator, S. N., and Lamm, M. E. (2001). A mucosal IgA-mediated excretory immune system in vivo. J. Immunol. 166:3688–3692.PubMedGoogle Scholar
  28. Russell, M. W., Brown, T. A., and Mestecky, J. (1981). Role of serum IgA: Hepatobiliary transport of circulating antigen. J. Exp. Med. 153:968–976.CrossRefPubMedGoogle Scholar
  29. Schneeman, T. A., Bruno, M. E. C., Schjerven, H., Johansen, F.-E., Chady, L., and Kaetzel, C. S. (2005). Regulation of the polymeric Ig receptor by signaling through TLRs 3 and 4: Linking innate and adaptive immune responses. J. Immunol. 175:376–384.PubMedGoogle Scholar
  30. Schwartz-Cornil, I., Benureau, Y., Greenberg, H., Hendrickson, B. A., and Cohen, J. (2002). Heterologous protection induced by the inner capsid proteins of rotavirus requires transcytosis of mucosal immunoglobulins. J. Virol. 76:8110–8117.CrossRefPubMedGoogle Scholar
  31. Sixbey, J. W., and Yao, Q.-Y. (1992). Immunoglobulin A-induced shift of Epstein-Barr virus tissue tropism. Science 255:1578–1580.CrossRefPubMedGoogle Scholar
  32. Socken, D. J., Simms, E. S., Nagy, B. R., Fisher, M. M., and Underdown, B. J. (1981). Secretory component-dependent hepatic transport of IgA antibody-antigen complexes. J. Immunol. 127:316–319.PubMedGoogle Scholar
  33. Sollid, L. M., Kvale, D., Brandtzaeg, P., Markussen, G., and Thorsby, E. (1987). Interferon-I enhances expression of secretory component, the epithelial receptor for polymeric immunoglobulins. J. Immunol. 138:4303–4306.PubMedGoogle Scholar
  34. Takada, A., Matsushita, S., Ninomiya, A., Kawaoka, Y., and Kida, H. (2003). Intranasal immunization with formalin-inactivated virus vaccine induces a broad spectrum of heterosubtypic immunity against influenza A virus infection in mice. Vaccine 21:3212–3218.CrossRefPubMedGoogle Scholar
  35. Tamer, C. M., Lamm, M. E., Robinson, J. K, Piskurich, J. F., and Kaetzel, C. S. (1995). Comparative studies of transcytosis and assembly of secretory IgA in Madin-Darby canine kidney cells expressing human polymeric Ig receptor. J Immunol. 155:707–714.PubMedGoogle Scholar
  36. Wright, A., Yan, H., Lamm, M. E., and Huang, Y. T. (2006). Immunoglobulin A antibodies against internal HIV-1 proteins neutralize HIV-1 replication inside epithelial cells. Virology 356:165–170.CrossRefPubMedGoogle Scholar
  37. Yan, H., Lamm, M. E., Bjorling, E., and Huang, Y. T. (2002). Multiple functions of IgA in mucosal defense against viruses: An in vitro measles virus model. J. Virol. 76:10972–10979.CrossRefPubMedGoogle Scholar
  38. Youngman, K. R., Fiocchi, C., and Kaetzel, C. S. (1994). Inhibition of IFN-Y activity in supernatants from stimulated human intestinal mononuclear cells prevents up-regulation of the polymeric Ig receptor in an intestinal epithelial cell-line. J. Immunol. 153:675–681.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Michael E. Lamm
    • 1
  1. 1.Department of PathologyCase Western Reserve UniversityClevelandUSA

Personalised recommendations