Biochemistry (Moscow)

, Volume 79, Issue 12, pp 1273–1285 | Cite as

Innate immunity underlies symbiotic relationships

  • E. P. KisselevaEmail author


Here, the modern data regarding interactions between normal microbiota and barrier tissues in plants, humans and animals are reviewed. The main homeostatic mechanisms responsible for interactions between epithelium and innate immune cells with symbiotic bacteria are described. A key step in this process is recognition of soluble microbial products by ligation to pattern-recognition receptors expressed on the host cells. As a result, epithelial cells secrete mucus, antibacterial peptides and immunoregulatory molecules. The main outcomes from immunological reactions towards symbiotic bacteria involve development of conditions for formation and maintenance of microbial biocenosis as well as providing safety for the host. Also, it is considered important to preserve and transfer beneficial bacteria to progeny.

Key words

normal microbiota pattern-recognition receptors epithelium innate immunity symbiotic relationships 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Whitman, W. B., Coleman, D. C., and Wiebe, W. J. (1998) Prokaryotes: the unseen majority, Proc. Natl. Acad. Sci. USA, 95, 6578–6583.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    McFall-Ngai, M. (2007) Care for the community, Nature, 445, 153.PubMedCrossRefGoogle Scholar
  3. 3.
    Klimovich, V. B. (2002) Actual problems of evolutionary immunology, J. Evol. Biochem. Physiol., 38, 562–574.CrossRefGoogle Scholar
  4. 4.
    Brown, E. M., Sadarangani, M., and Finlay, B. B. (2013) The role of the immune system in governing host-microbe interactions in the intestine, Nature Immunol., 14, 660–667.CrossRefGoogle Scholar
  5. 5.
    Hill, D. A., and Artis, D. (2010) Intestinal bacteria and the regulation of immune cell homeostasis, Annu. Rev. Immunol., 28, 623–667.PubMedCrossRefGoogle Scholar
  6. 6.
    Josefowicz, S. Z., Lu, L.-F., and Rudensky, A. Y. (2012) Regulatory T cells: mechanism of differentiation and function, Annu. Rev. Immunol., 30, 531–564.PubMedCrossRefGoogle Scholar
  7. 7.
    Feldhaar, H., and Gross, R. (2009) Genome degeneration affects both extracellular and intracellular bacterial endosymbionts, J. Biol., 8, 31.1–31.5.CrossRefGoogle Scholar
  8. 8.
    Fernandez, L., Langa, S., Martin, V., Maldonaldo, A., Jimenez, E., Martin, R., and Rodriguez, J. M. (2013) The human milk microbiota: origin and potential roles in health and disease, Pharmacol. Res., 69, 1–10.PubMedCrossRefGoogle Scholar
  9. 9.
    Koropatnick, T. A., Engle, J. T., Apicella, M. A., Stabb, E. V., Goldman, W. E., and McFall-Ngai, M. J. (2004) Microbial factor-mediated development in a host-bacterial mutualism, Science, 306, 1186–1188.PubMedCrossRefGoogle Scholar
  10. 10.
    Wang, Y., and Ruby, E. G. (2011) The roles of NO in microbial symbioses, Cell. Microbiol., doi: 10.1111/j.1462-5822.2011.01576.x.Google Scholar
  11. 11.
    Nyholm, S. V., and Graf, J. (2012) Knowing your friends: invertebrate innate immunity fosters beneficial bacterial symbioses, Nature Rev. Microbiol., 10, 815–827.CrossRefGoogle Scholar
  12. 12.
    Medzhitov, R., and Janeway, C. A. (2002) Decoding the patterns of self and nonself by innate immune system, Science, 296, 298–300.PubMedCrossRefGoogle Scholar
  13. 13.
    Ferguson, B. J., Indrasumunar, A., Hayashi, S., Lin, M.-H., Lin, Y.-H., Reld, D. E., and Gresshoff, P. M. (2010) Molecular analysis of legume nodule development and autoregulation, J. Integr. Plant Biol., 52, 61–76.PubMedCrossRefGoogle Scholar
  14. 14.
    Renz, H., Brandtzaeg, P., and Hornef, M. (2012) The impact of perinatal immune development of mucosal homeostasis and chronic inflammation, Nature Rev. Immunol., 12, 9–23.Google Scholar
  15. 15.
    Hooper, J. V., and Gordon, J. L. (2001) Commensal host-bacterial relationships in the gut, Science, 292, 1115–1118.PubMedCrossRefGoogle Scholar
  16. 16.
    Stappenbeck, S., Hooper, L. V., and Gordon, J. I. (2002) Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells, Proc. Natl. Acad. Sci. USA, 99, 15451–15455.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Hooper, L. V., Stappenbeck, T. S., Hong, C. V., and Gordon, J. I. (2003) Angiogenins: a new class of microbicidal proteins involved in innate immunity, Nat. Immunol., 4, 269–273.PubMedCrossRefGoogle Scholar
  18. 18.
    Bollinger, R. R., Barbas, A. S., Bush, E. L., Lin, S. S., and Parker, W. (2007) Biofilms in the large bowel suggest an apparent function of the human vermiform appendix, J. Theor. Biol., 249, 826–831.CrossRefGoogle Scholar
  19. 19.
    Laurin, M., Everett, M. L., and Parker, W. (2011) The cecal appendix: one more immune component with a function disturbed by post-industrial culture, Anat. Record., 294, 567–579.CrossRefGoogle Scholar
  20. 20.
    Atuma, C., Strugala, V., Allen, A., and Holm, L. (2001) The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo, Am. J. Physiol. Gastrointest. Liver Physiol., 280, G922–G929.PubMedGoogle Scholar
  21. 21.
    Johansson, M. E. V., Phillipson, M., Petersson, J., Velcich, A., Holm, L., and Hansson, G. C. (2008) The inner of the two Muc2 mucin-dependent mucus layers in colon devoid of bacteria, Proc. Natl. Acad. Sci. USA, 105, 15064–15069.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Johansson, M. E. V., Holmen Larsson, J. M., and Hansson, G. C. (2011) The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions, Proc. Natl. Acad. Sci. USA, 108,Suppl. 1, 4659–4665.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Shan, M., Gentile, M., Yeiser, J. R., Walland, A. C., Bornstein, V. U., Chen, K., He, B., Cassis, L., Bigas, A., Cols, M., Comerma, L., Huang, B., Blander, J. M., Xiong, H., Mayer, L., Berin, C., Augenlicht, L. H., Velcich, A., and Cerutti, A. (2013) Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals, Science, 342, 447–453.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Frantz, A. L., Rogier, E. W., Weber, C. R., Shen, L., Cohen, D. A., Fenton, L. F., Bruno, M. E. C., and Kaetzel, C. S. (2012) Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with down-regulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides, Mucosal Immunol., 5, 501–512.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Burger-van Paassen, N., Vincent, A., Puiman, P. J., van der Sluis, M., Bouma, J., Boehm, G., van Goudoever, J. B., van Seuningen, I., and Renes, I. B. (2009) The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection, Biochem. J., 420, 211–219.PubMedCrossRefGoogle Scholar
  26. 26.
    Steenwinckel, V., Louahed, J., Lemaire, M. M., Sommereyns, C., Warnier, G., McKenzie, A., Brombacher, F., Van Snick, J., and Renauld, J.-C. (2009) IL-9 promotes IL-13-dependent Paneth cell hyperplasia and up-regulation of innate immunity mediators in intestinal mucosa, J. Immunol., 182, 4737–4743.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhao, P., Xiao, X., Ghobrial, R. M., and Li, X. C. (2013) IL-9 and Th9 cells: progress and challenges, Intern. Immunol., 25, 547–551.CrossRefGoogle Scholar
  28. 28.
    Salzman, N. H. (2011) Microbiota-immune system interaction: an uneasy alliance, Curr. Opin. Microbiol., 14, 99–105.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Kokryakov, V. N. (2006) Essays about the Innate Immunity [in Russian], Nauka, St. Petersburg.Google Scholar
  30. 30.
    Putsep, K., Axelsson, L. G., Boman, A., Midtvedt, T., Normark, S., Boman, H. G., and Andersson, M. (2000) Germ-free and colonized mice generate the same products from enteric prodefensins, J. Biol. Chem., 275, 40478–40482.PubMedCrossRefGoogle Scholar
  31. 31.
    Karlsson, J., Putsep, K., Chu, H., Kays, R. J., Bevins, C. L., and Andersson, M. (2008) Regional variations in Paneth cell antimicrobial peptide expression along mouse intestinal tract, BMC Immunol., 9, 37.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Menendez, A., Willing, B. P., Montero, M., Wlodarska, M., So, C. C., Bhinder, G., Vallance, B. A., and Finlay, B. B. (2013) Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic expression of ileal Paneth cell α-defensins, J. Innate Immun., 5, 39–49.PubMedCrossRefGoogle Scholar
  33. 33.
    Kobayashi, K. S., Chamaillard, M., Ogura, Y., Henegariu, O., Inohara, N., Nunez, G., and Flavell, R. A. (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract, Science, 307, 731–734.PubMedCrossRefGoogle Scholar
  34. 34.
    Cash, H. L., Whitham, C. V., Behrendt, C. L., and Hooper, L. V. (2006) Symbiotic bacteria direct expression of an intestinal bacterial lectin, Science, 313, 1052–1054.CrossRefGoogle Scholar
  35. 35.
    Sanos, S. L., Bui, V. L., Mortha, A., Oberle, K., Heners, C., Johner, C., and Diefenbach, A. (2009) POPγt and commensal microflora are required for the differentiation of mucosal interleukin-22 producing NKp46+ cells, Nat. Immunol., 10, 11–12.CrossRefGoogle Scholar
  36. 36.
    Brandl, K., Pitas, G., Schnabl, B., DeMatteo, R. P., and Pamer, E. G. (2007) MyD88-mediated signals induce the bacterial lectin RegIIIγ and protect mice against intestinal Listeria monocytogenes infection, J. Exp. Med., 204, 1891–1900.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Otto, M. (2006) Bacterial evasion of antimicrobial peptides by biofilm formation, Curr. Top. Microbiol. Immunol., 306, 251–258.PubMedGoogle Scholar
  38. 38.
    Bevins, C. L., and Ganz, T. (2004) Antimicrobial peptides of the alimentary tract of animals, in Mammalian Host Defense Peptides (Diamond, G., Laute, D., and Klein-Paul, M., eds.) Cambridge University, UK, pp. 161–188.Google Scholar
  39. 39.
    Scott, M. G., Davidson, D. J., Gold, M. R., Bowdish, D., and Hancock, R. E. W. (2002) The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses, J. Immunol., 169, 3883–3891.PubMedCrossRefGoogle Scholar
  40. 40.
    Masuda, K., Nakamura, K., Yoshioka, S., Fukaya, R., Sakai, N., and Ayabe, T. (2011) Regulation of microbiota by antimicrobial peptides in the gut, Adv. Otorhinolaryngol., 72, 97–99.PubMedGoogle Scholar
  41. 41.
    Weaver, C. T., and Hatton, R. D. (2009) Interplay between the Th17 and Treg cell lineages: a (co)evolutionary perspective, Nat. Rev. Immunol., 9, 883–889.PubMedCrossRefGoogle Scholar
  42. 42.
    Matzinger, P. (2007) Friendly and dangerous signals: is the tissue in control? Nat. Immunol., 8, 11–13.PubMedCrossRefGoogle Scholar
  43. 43.
    Turner, J. R. (2009) Intestinal mucosal barrier function in health and disease, Nat. Rev. Immunol., 9, 799–809.PubMedCrossRefGoogle Scholar
  44. 44.
    Pickard, J. M., and Chervonsky, A. V. (2010) Sampling of the intestinal microbiota by epithelial M cells, Curr. Gastroenterol. Rep., 12, 331–339.PubMedCrossRefGoogle Scholar
  45. 45.
    Everett, M. L., Palestrant, D., Miller, S. E., Bollinger, R. R., and Parker, W. (2004) Immune exclusion and immune inclusion: a new model of host-bacterial interactions in the gut, Clin. Appl. Immunol. Rev., 4, 321–332.CrossRefGoogle Scholar
  46. 46.
    Macia, L., Thorburn, A. N., Binge, L. C., Marino, E., Rogers, K. E., Maslowski, K. M., Vieira, A. T., Kranich, J., and Mackay, C. R. (2012) Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases, Immunol. Rev., 245, 164–176.PubMedCrossRefGoogle Scholar
  47. 47.
    Kruglov, A. A., Grivennikov, S. I., Kuprash, D. V., Winsauer, C., Prepens, S., Seleznik, G. M., Ebert, G., Littman, D. R., Heikenwalder, M., Tumanov, A. V., and Nedospasov, S. A. (2013) Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis, Science, 342, 1243–1246.PubMedCrossRefGoogle Scholar
  48. 48.
    Pearson, C., Uhlig, H. H., and Powrie, F. (2012) Lymphoid microenvironments and innate lymphoid cells in the gut, Trends Immunol., 33, 289–296.PubMedCrossRefGoogle Scholar
  49. 49.
    Sonnenberg, G. F., Fouser, L. A., and Artis, D. (2011) Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22, Nat. Immunol., 12, 383–390.PubMedCrossRefGoogle Scholar
  50. 50.
    Macpherson, A. J., Geuking, M. B., and McCoy, K. D. (2012) Homeland security: IgA immunity at the frontiers of the body, Trends Immunol., 33, 160–167.PubMedCrossRefGoogle Scholar
  51. 51.
    Hepworth, M. R., Montichelli, L. A., Fung, T. C., Ziegler, C. G. K., Grunberg, S., Sinha, R., Mantegazza, A. R., Ma, H.-L., Crawford, A., Angelosanto, J. M., Wherry, E. J., Koni, P. A., Bushman, F. D., Elson, C. O., Eberl, G., Artis, D., and Sonnenberg, G. F. (2013) Innate lymphoid cells regulate CD4+ T-cell responses to intestinal bacteria, Nature, 498, 113–117.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Smith, P. D., Smythies, L. E., Shen, R., Greenwell-Wild, T., Gliozzi, M., and Wahl, S. M. (2011) Intestinal macrophages and response to microbial encroachment, Immunology, 4, 31–42.Google Scholar
  53. 53.
    Honda, K., and Takeda, K. (2009) Regulatory mechanisms of immune responses to intestinal bacteria, Mucosal Immunol., 2, 187–196.PubMedCrossRefGoogle Scholar
  54. 54.
    Pena, J. A., and Versalovic, J. (2003) Lactobacillus rhamnosus GG decreases TNF-α production in lipopolysaccharide-activated murine macrophages by contact-independent mechanism, Cell. Microbiol., 5, 277–285.PubMedCrossRefGoogle Scholar
  55. 55.
    Iliev, I. D., Mileti, E., Matteoli, G., Chieppa, M., and Rescigno, M. (2009) Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning, Mucosal Immunol., 2, 340–350.PubMedCrossRefGoogle Scholar
  56. 56.
    Mantis, N. J., Rol, N., and Corthesy, B. (2011) Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut, Mucosal Immunol., 4, 603–611.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Han, D., Walsh, M. C., Cejas, P. J., Dang, N. N., Kim, Y. F., Kim, J., Charrier-Hisamuddin, L., Chau, L., Zhang, Q., Bittinger, K., Bushman, F. D., Turka, L. A., Shen, H., Reizis, B., DeFranco, A. L., Wu, G. D., and Choi, Y. (2013) Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance, Immunity, 28, 1–12.Google Scholar
  58. 58.
    Pabst, O. (2012) New concepts in the generation and functions of IgA, Nat. Rev. Immunol., 25, 139–143.Google Scholar
  59. 59.
    Snoeck, V., Peters, I. E., and Cox, E. (2006) The IgA system: a comparison of structure and function in different species, Vet. Res., 37, 455–467.PubMedCrossRefGoogle Scholar
  60. 60.
    He, B., Xu, W., Santini, P. A., Polydorides, A. D., Chiu, A., Estrella, J., Shan, M., Shadbun, A., Villanacci, V., Plebani, A., Knowles, D. M., Rescigno, M., and Cerutti, A. (2007) Intestinal bacteria trigger T-cell-independent IgA2 class switching by inducing epithelial cell secretion of the cytokine APRIL, Immunity, 26, 812–826.PubMedCrossRefGoogle Scholar
  61. 61.
    Brandtzaeg, P. (2013) Secretory IgA: designed for anti-microbial defense, Front. Immunol., 4, 1–17.CrossRefGoogle Scholar
  62. 62.
    Attardo, G. M., Lohs, C., Heddi, A., Alam, U. H., Yildirim, S., and Aksoy, S. (2008) Analysis of milk gland structure and function in Glossina morsitans: milk protein production, symbiont populations and fecundity, Insect. Physiol., 54, 1236–1242.CrossRefGoogle Scholar
  63. 63.
    Cabrera-Rubio, R., Collado, M. C., Laitinen, K., Salminen, S., Isolauri, E., and Mira, A. (2012) The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery, Am. J. Clin. Nutr., 96, 544–551.PubMedCrossRefGoogle Scholar
  64. 64.
    Field, C. J. (2005) The immunological components of human milk and their effect on immune development in infants, J. Nutr., 135, 1–4.PubMedGoogle Scholar
  65. 65.
    Chirico, G., Marzollo, R., Cortinovis, S., Fonte, C., and Gasparoni, A. (2008) Antiinfective properties of human milk, J. Nutr., 138, 1801S–1806S.PubMedGoogle Scholar
  66. 66.
    Arvola, M., Gustafsson, E., Svensson, L., Jansson, L., Holmdahl, R., Heyman, B., Okabe, M., and Mattsson, R. (2000) Immunoglobulin-secreting cells of maternal origin can be detected in B cell-deficient mice, Biol. Reprod., 63, 1817–1824.PubMedCrossRefGoogle Scholar
  67. 67.
    Mathias, A., and Corthesy, B. (2011) N-glycans on secretory component. Mediators of the interaction between secretory IgA and Gram-positive commensals sustaining intestinal homeostasis, Gut Microbes, 2, 287–293.PubMedCrossRefGoogle Scholar
  68. 68.
    Oda, H., Wakabayashi, H., Yamauchi, K., and Abe, F. (2014) Lactoferrin and bifidobacteria, Biometals, 27, 915–922.PubMedCrossRefGoogle Scholar
  69. 69.
    Husson, M. O., Legrand, D., Spik, G., and Leclerc, H. (1993) Iron acquisition by Helicobacter pylori: importance of human lactoferrin, Infect. Immun., 61, 2694–2697.PubMedCentralPubMedGoogle Scholar
  70. 70.
    Blaser, M. (2011) Stop the killing of beneficial bacteria, Nature, 476, 393–394.PubMedCrossRefGoogle Scholar
  71. 71.
    Chen, Y., and Blaser, M. J. (2007) Inverse associations of Helicobacter pylori with asthma and allergy, Arch. Intern. Med., 167, 821–827.PubMedCrossRefGoogle Scholar
  72. 72.
    He, Y., Liu, S., Leone, S., and Newburg, D. S. (2014) Human colostrum oligosaccharides modulate major immunologic pathways of immature human intestine, Mucosal Immunol., doi: 10.1038/mi.2014.20 (Epub ahead of print).Google Scholar
  73. 73.
    Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaheh, F., Edberg, S., and Medzhitov, R. (2004) Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis, Cell, 118, 229–241.PubMedCrossRefGoogle Scholar
  74. 74.
    Goto, Y., and Ivanov, I. I. (2013) Intestinal epithelial cells as mediators of the commensal-host immune crosstalk, Immunol. Cell Biol., 91, 204–214.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  1. 1.Institute of Experimental MedicineRussian Academy of Medical SciencesSt. PetersburgRussia

Personalised recommendations