Browse > Article
http://dx.doi.org/10.4110/in.2012.12.5.165

Mucosal Immune System and M Cell-targeting Strategies for Oral Mucosal Vaccination  

Kim, Sae-Hae (Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Chonbuk National University)
Lee, Kyung-Yeol (Department of Oral Microbiology and Institute of Oral Bioscience, Chonbuk National University)
Jang, Yong-Suk (Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Chonbuk National University)
Publication Information
IMMUNE NETWORK / v.12, no.5, 2012 , pp. 165-175 More about this Journal
Abstract
Vaccination is one of the most effective methods available to prevent infectious diseases. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganisms, are one of the first areas where infections are established, and therefore have frontline status in immunity, making mucosa ideal sites for vaccine application. Moreover, vaccination through the mucosal immune system could induce effective systemic immune responses together with mucosal immunity in contrast to parenteral vaccination, which is a poor inducer of effective immunity at mucosal surfaces. Among mucosal vaccines, oral mucosal vaccines have the advantages of ease and low cost of vaccine administration. The oral mucosal immune system, however, is generally recognized as poorly immunogenic due to the frequent induction of tolerance against orally-introduced antigens. Consequently, a prerequisite for successful mucosal vaccination is that the orally introduced antigen should be transported across the mucosal surface into the mucosa-associated lymphoid tissue (MALT). In particular, M cells are responsible for antigen up-take into MALT, and the rapid and effective transcytotic activity of M cells makes them an attractive target for mucosal vaccine delivery, although simple transport of the antigen into M cells does not guarantee the induction of specific immune responses. Consequently, development of mucosal vaccine adjuvants based on an understanding of the biology of M cells has attracted much research interest. Here, we review the characteristics of the oral mucosal immune system and delineate strategies to design effective oral mucosal vaccines with an emphasis on mucosal vaccine adjuvants.
Keywords
Adjuvant; Complement 5a receptor; Mucosal immune system; Vaccine;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Keely, S., L. E. Glover, T. Weissmueller, C. F. MacManus, S. Fillon, B. Fennimore, and S. P. Colgan. 2010. Hypoxia-inducible factor-dependent regulation of platelet-activating factor receptor as a route for gram-positive bacterial translocation across epithelia. Mol. Biol. Cell. 21: 538-546.
2 Tyrer, P., A. R. Foxwell, A. W. Cripps, M. A. Apicella, and J. M. Kyd. 2006. Microbial pattern recognition receptors mediate M-cell uptake of a gram-negative bacterium. Infect. Immun. 74: 625-631.
3 Hoft, D. F, V. Brusic, and I. G. Sakala. 2011. Optimizing vaccine development. Cell. Microbiol. 13: 934-942.
4 McAleer, J. P. and J. K. Kolls. 2011. Mechanisms controlling Th17 cytokine expression and host defense. J. Leukoc. Biol. 90: 263-270.
5 Blaschitz, C. and M. Raffatellu. 2010. Th17 cytokines and the gut mucosal barrier. J. Clin. Immunol. 30: 196-203.
6 Sheridan, B. S. and L. Lefrançois. 2011. Regional and mucosal memory T cells. Nat. Immunol. 12: 485-491.
7 Borges, O., F. Lebre, D. Bento, G. Borchard, and H. E. Junginger. 2010. Mucosal vaccines: recent progress in understanding the natural barriers. Pharm. Res. 27: 211-223.
8 Cho, K. A., J. E. Cha, and S. Y. Woo. 2008. Oral tolerance increased the proportion of CD8+ T cells in mouse intestinal lamina propria. Immune Netw. 8: 46-52.
9 Rescigno, M., U. Lopatin, and M. Chieppa. 2008. Interactions among dendritic cells, macrophages, and epithelial cells in the gut: implications for immune tolerance. Curr. Opin. Immunol. 20: 669-675.
10 Czerkinsky, C. and J. Holmgren. 2012. Mucosal delivery routes for optimal immunization: targeting immunity to the right tissues. Curr. Top. Microbiol. Immunol. 354: 1-18.
11 Mora, J. R., M. Iwata, B. Eksteen, S. Y. Song, T. Junt, B. Senman, K. L. Otipoby, A. Yokota, H. Takeuchi, P. Ricciardi-Castagnoli, K. Rajewsky, D. H. Adams, and U. H. von Andrian. 2006. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314: 1157-1160.
12 Iwata, M., A. Hirakiyama, Y. Eshima, H. Kagechika, C. Kato, and S. Y. Song. 2004. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21: 527-538.
13 Pavot, V., N. Rochereau, C. Genin, B. Verrier, and S. Paul. 2012. New insights in mucosal vaccine development. Vaccine 30: 142-154.
14 Mestecky, J., H. Nguyen, C. Czerkinsky, and H. Kiyono. 2008. Oral immunization: an update. Curr. Opin. Gastroenterol. 24: 713-719.
15 Sturm, J. T., M. E. Carr, M. G. Luxenberg, J. K. Swoyer, and J. J. Cicero. 1990. The prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis in victims of sexual assault. Ann. Emerg. Med. 19: 587-590.
16 Streatfield, S. J. and J. A. Howard. 2003. Plant-based vaccines. Int. J. Parasitol. 33: 479-493.
17 Walmsley, A. M. and C. J. Arntzen. 2000. Plants for delivery of edible vaccines. Curr. Opin. Biotechnol. 11: 126-129.
18 Haq, T. A., H. S. Mason, J. D. Clements, and C. J. Arntzen. 1995. Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 268: 714-716.
19 Yuki, Y., D. Tokuhara, T. Nochi, H. Yasuda, M. Mejima, S. Kurokawa, Y. Takahashi, N. Kataoka, U. Nakanishi, Y. Hagiwara, K. Fujihashi, F. Takaiwa, and H. Kiyono. 2009. Oral MucoRice expressing double-mutant cholera toxin A and B subunits induces toxin-specific neutralising immunity. Vaccine 27: 5982-5988.
20 Heath, J. P. 1996. Epithelial cell migration in the intestine. Cell. Biol. Int. 20: 139-146.
21 Gebert, A., S. Fassbender, K. Werner, and A. Weissferdt. 1999. The development of M cells in Peyer's patches is restricted to specialized dome-associated crypts. Am. J. Pathol. 154:1573-1582.
22 Hsieh, E. H., X. Fernandez, J. Wang, M. Hamer, S. Calvillo, M. Croft, B. S. Kwon, and D. D. Lo. 2010. CD137 is required for M cell functional maturation but not lineage commitment. Am. J. Pathol. 177: 666-676.
23 Knoop, K. A., N. Kumar, B. R. Butler, S. K. Sakthivel, R. T. Taylor, T. Nochi, H. Akiba, H. Yagita, H. Kiyono, and I. R. Williams. 2009. RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium. J. Immunol. 183: 5738-5747.
24 Mach, J., T. Hshieh, D. Hsieh, N. Grubbs, and A. Chervonsky. 2005. Development of intestinal M cells. Immunol. Rev. 206: 177-189.
25 Finzi, G., M. Cornaggia, C. Capella, R. Fiocca, F. Bosi, E. Solcia, and I. M. Samloff. 1993. Cathepsin E in follicle associated epithelium of intestine and tonsils: localization to M cells and possible role in antigen processing. Histochemistry 99: 201-211.
26 Clark, M. A. and M. A. Jepson. 2003. Intestinal M cells and their role in bacterial infection. Int. J. Med. Microbiol. 293: 17-39.
27 Pickard, J. M. and A. V. Chervonsky. 2010. Sampling of the intestinal microbiota by epithelial M cells. Curr. Gastroenterol. Rep. 12: 331-339.
28 Azizi, A., A. Kumar, F. Diaz-Mitoma, and J. Mestecky. 2010. Enhancing oral vaccine potency by targeting intestinal M cells. PLoS Pathog. 6: e1001147.
29 Kernéis, S., A. Bogdanova, J. P. Kraehenbuhl, and E. Pringault. 1997. Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria. Science 277: 949-952.
30 Gullberg, E., M. Leonard, J. Karlsson, A. M. Hopkins, D. Brayden, A. W. Baird, and P. Artursson. 2000. Expression of specific markers and particle transport in a new human intestinal M-cell model. Biochem. Biophys. Res. Commun. 279: 808-813.
31 Brandtzaeg, P., H. Kiyono, R. Pabst, and M. W. Russell. 2008. Terminology: nomenclature of mucosa-associated lymphoid tissue. Mucosal Immunol. 1: 31-37.
32 Brandtzaeg, P. 2009. Mucosal immunity: induction, dissemination, and effector functions. Scand. J. Immunol. 70: 505-515.
33 Otczyk, D. C. and A. W. Cripps. 2010. Mucosal immunization: a realistic alternative. Hum. Vaccin. 6: 978-1006.
34 Bemark, M., P. Boysen, and N. Y. Lycke. 2012. Induction of gut IgA production through T cell-dependent and T cell-independent pathways. Ann. N. Y. Acad. Sci. 1247:97-116.
35 Strugnell, R. A. and O. L. Wijburg. 2010. The role of secretory antibodies in infection immunity. Nat. Rev. Microbiol. 8: 656-667.
36 Cerutti, A., K. Chen, and A. Chorny. 2011. Immunoglobulin responses at the mucosal interface. Annu. Rev. Immunol. 29: 273-293.
37 Bevins, C. L. and N. H. Salzman. 2011. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat. Rev. Microbiol. 9:356-368.
38 Garrett, W. S., J. I. Gordon, and L. H. Glimcher. 2010. Homeostasis and inflammation in the intestine. Cell 140:859-870.
39 Heazlewood, C. K., M. C. Cook, R. Eri, G. R. Price, S. B. Tauro, D. Taupin, D. J. Thornton, C. W. Png, T. L. Crockford, R. J. Cornall, R. Adams, M. Kato, K. A. Nelms, N. A. Hong, T. H. Florin, C. C. Goodnow, and M. A. McGuckin. 2008. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med.5:e54.
40 Biton, M., A. Levin, M. Slyper, I. Alkalay, E. Horwitz, H. Mor, S. Kredo-Russo, T. Avnit-Sagi, G. Cojocaru, F. Zreik, Z. Bentwich, M. N. Poy, D. Artis, M. D. Walker, E. Hornstein, E. Pikarsky, and Y. Ben-Neriah. 2011. Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk. Nat. Immunol. 12: 239-246.
41 Kaser, A., M. Tomczak, and R. S. Blumberg. 2011. "ER stress(ed out)!": Paneth cells and ischemia-reperfusion injury of the small intestine. Gastroenterology 140:393-396.
42 Niederreiter, L. and A. Kaser. 2011. Endoplasmic reticulum stress and inflammatory bowel disease. Acta Gastroenterol. Belg. 74: 330-333.
43 Iliev, I. D., E. Mileti, G. Matteoli, M. Chieppa, and M. Rescigno. 2009. Intestinal epithelial cells promote colitis- protective regulatory T-cell differentiation through dendritic cell conditioning. Mucosal Immunol. 2:340-350.
44 Rimoldi, M., M. Chieppa, V. Salucci, F. Avogadri, A. Sonzogni, G. M. Sampietro, A. Nespoli, G. Viale, P. Allavena, and M. Rescigno. 2005. Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat. Immunol. 6:507-514.
45 He, B., W. Xu, P. A. Santini, A. D. Polydorides, A. Chiu, J. Estrella, M. Shan, A. Chadburn, V. Villanacci, A. Plebani, D. M. Knowles, M. Rescigno, and A. Cerutti. 2007. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 26:812-826.
46 Kyd, J. M. and A. W. Cripps. 2008. Functional differences between M cells and enterocytes in sampling luminal antigens. Vaccine, 26:6221-6224.
47 Nakato, G., K. Hase, M. Suzuki, M. Kimura, M. Ato, M. Hanazato, M. Tobiume, M. Horiuchi, R. Atarashi, N. Nishida, M. Watarai, K. Imaoka, and H. Ohno. 2012. Cutting Edge: Brucella abortus exploits a cellular prion protein on intestinal M cells as an invasive receptor. J. Immunol. 189: 1540-1544.
48 Jang, M. H., M. N. Kweon, K. Iwatani, M. Yamamoto, K. Terahara, C. Sasakawa, T. Suzuki, T. Nochi, Y. Yokota, P. D. Rennert, T. Hiroi, H. Tamagawa, H. Iijima, J. Kunisawa, Y. Yuki, and H. Kiyono. 2004. Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc. Natl. Acad. Sci. USA 101: 6110-6115.
49 Corr, S. C., C. C. Gahan, and C. Hill. 2008. M-cells: origin, morphology and role in mucosal immunity and microbial pathogenesis. FEMS Immunol. Med. Microbiol. 52: 2-12.
50 Owen, R. L. and A. L. Jones. 1974. Epithelial cell specialization within human Peyer's patches: an ultrastructural study of intestinal lymphoid follicles. Gastroenterology 66:189-203
51 Kim, S. H., D. I. Jung, I. Y. Yang, J. Kim, K. Y. Lee, T. Nochi, H. Kiyono, and Y. S. Jang. 2011. M cells expressing the complement C5a receptor are efficient targets for mucosal vaccine delivery. Eur. J. Immunol. 41: 3219-3229.
52 Kunisawa, J., Y. Kurashima, and H. Kiyono. 2012. Gut-associated lymphoid tissues for the development of oral vaccines. Adv. Drug. Deliv. Rev. 64: 523-530.
53 Pasetti, M. F., J. K. Simon, M. B. Sztein, and M. M. Levine. 2011. Immunology of gut mucosal vaccines. Immunol. Rev. 239: 125-148.
54 Weiner, H. L., A. P. da Cunha, F. Quintana, and H. Wu. 2011. Oral tolerance. Immunol. Rev. 241: 241-259.
55 Lycke, N. 2012. Recent progress in mucosal vaccine development: potential and limitations. Nat. Rev. Immunol. 12: 592-605.
56 Ogra, P. L. 2003. Mucosal immunity: some historical perspective on host-pathogen interactions and implications for mucosal vaccines. Immunol. Cell. Biol. 81: 23-33.
57 Artis, D. 2008. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat. Rev. Immunol. 8: 411-420.
58 McGuckin, M. A., S. K. Lindén, P. Sutton, and T. H. Florin. 2011. Mucin dynamics and enteric pathogens. Nat. Rev. Microbiol. 9: 265-278.
59 Wells, J. M., O. Rossi, M. Meijerink, and P. van Baarlen. 2011. Epithelial crosstalk at the microbiota-mucosal interface. Proc. Natl. Acad. Sci. USA 108 Suppl 1:4607-4614.
60 Iwasaki, A. 2007. Mucosal dendritic cells. Annu. Rev. Immunol. 25:381-418.
61 Hase, K., K. Kawano, T. Nochi, G. S. Pontes, S. Fukuda, M. Ebisawa, K. Kadokura, T. Tobe, Y. Fujimura, S. Kawano, A. Yabashi, S. Waguri, G. Nakato, S. Kimura, T. Murakami, M. Iimura, K. Hamura, S. Fukuoka, A. W. Lowe, K. Itoh, H. Kiyono, and H. Ohno. 2009. Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response. Nature 462: 226-230.
62 Kim, S. H., K. W. Seo, J. Kim, K. Y. Lee, and Y. S. Jang. 2010. The M cell-targeting ligand promotes antigen delivery and induces antigen-specific immune responses in mucosal vaccination. J. Immunol. 185: 5787-5795.
63 Clark, M. A., B. H. Hirst, and M. A. Jepson. 1998. M-cell surface beta1 integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer's patch M cells. Infect. Immun. 66: 1237-1243.
64 Wolf, J. L., R. S. Kauffman, R. Finberg, R. Dambrauskas, B. N. Fields, and J. S. Trier. 1983. Determinants of reovirus interaction with the intestinal M cells and absorptive cells of murine intestine. Gastroenterology 85: 291-300.
65 Chen, K. and A. Cerutti. 2010. Vaccination strategies to promote mucosal antibody responses. Immunity. 33: 479-491.
66 Almond, J. W. 2007. Vaccine renaissance. Nat. Rev. Microbiol. 5:478-481.
67 Rappuoli, R., C. W. Mandl, S. Black, and E. De Gregorio. 2011. Vaccines for the twenty-first century society. Nat. Rev. Immunol. 11:865-872.
68 Mitragotri, S. 2005. Immunization without needles. Nat. Rev. Immunol. 5: 905-916.
69 Shin, S., S. N. Desai, B. K. Sah, and J. D. Clemens. 2011. Oral vaccines against cholera. Clin. Infect. Dis. 52:1343-1349.
70 Czerkinsky, C. and J. Holmgren. 2009. Enteric vaccines for the developing world: a challenge for mucosal immunology. Mucosal Immunol. 2: 284-287.
71 Coffman, R. L., A. Sher, and R. A. Seder. 2010. Vaccine adjuvants: putting innate immunity to work. Immunity 33: 492-503.
72 Gebert, A., H. J. Rothkötter, and R. Pabst. 1996. M cells in Peyer's patches of the intestine. Int. Rev. Cytol. 167: 91-159.
73 Reed, S. G., S. Bertholet, R. N. Coler, and M. Friede. 2009. New horizons in adjuvants for vaccine development. Trends Immunol. 30: 23-32.
74 Babai, I., S. Samira, Y. Barenholz, Z. Zakay-Rones, and E Kedar. 1999. A novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/neuraminidase and IL-2 or GM-CSF. II. Induction of TH1 and TH2 responses in mice. Vaccine 17: 1239-1250.
75 Kuolee, R. and W. Chen. 2008. M cell-targeted delivery of vaccines and therapeutics. Expert Opin. Drug. Deliv. 5: 693-702.
76 Foster, N., M. A. Clark, M. A. Jepson, and B. H. Hirst. 1998. Ulex europaeus 1 lectin targets microspheres to mouse Peyer's patch M-cells in vivo. Vaccine 16: 536-541.
77 Clark, M. A., M. A. Jepson, N. L. Simmons, and B. H. Hirst. 1994. Differential surface characteristics of M cells from mouse intestinal Peyer's and caecal patches. Histochem. J. 26: 271-280.
78 Gupta, P. N., K. Khatri, A. K. Goyal, N. Mishra, and S. P. Vyas. 2007. M-cell targeted biodegradable PLGA nanoparticles for oral immunization against hepatitis B. J. Drug. Target. 15: 701-713.
79 Clark, M. A., H. Blair, L. Liang, R. N. Brey, D. Brayden, and B. H. Hirst. 2001. Targeting polymerised liposome vaccine carriers to intestinal M cells. Vaccine 20: 208-217.
80 Devriendt, B., B. G. De Geest, B. M. Goddeeris, and E. Cox. 2012. Crossing the barrier: Targeting epithelial receptors for enhanced oral vaccine delivery. J. Control Release. 160: 431-439.
81 Nochi, T., Y. Yuki, A. Matsumura, M. Mejima, K. Terahara, D. Y. Kim, S. Fukuyama, K. Iwatsuki-Horimoto, Y. Kawaoka, T. Kohda, S. Kozaki, O. Igarashi, and H. Kiyono. 2007. A novel M cell-specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses. J. Exp. Med. 204: 2789-2796.
82 Hirabayashi, J., T. Hashidate, Y. Arata, N. Nishi, T. Nakamura, M. Hirashima, T. Urashima, T. Oka, M. Futai, W. E. Muller, F. Yagi, and K. Kasai. 2002. Oligosaccharide specificity of galectins: a search by frontal affinity chromatography. Biochim. Biophys. Acta. 1572: 232-254.