Mucosal immune system of digestive and respiratory tracts: possibilities of prevention and treatment of infectious diseases

The immune system of the body’s mucous membranes plays a huge role in the development, maintenance and regulation of immune homeostasis, being an important component of the multi-component immune system. The structural basis of local immunity is the lymphatic tissue associated with the mucous membranes (MALT). There is now scientific evidence that the mucous membrane sections of different body systems interact closely with each other, subject to the same regulatory influences. This relationship is particularly close between the digestive and respiratory tract, and studies have shown that vaccination of the mucosa of one part increases the protective function of the mucosa of another part, and that virus infection leads to virus-specific concentrations of immunoglobulins in the secretion of the mucosa of another part. The impact on the intestinal microbiota can be a convenient tool to prevent not only gastrointestinal, but also respiratory diseases. In a number of works the clinical effects confirming expediency of probiotics application both at healthy, and at sick children are confirmed. An extremely important component of the local immune system is the antimicrobial peptides, which play a key role in the formation of the first line of defense against infections. AMP have a number of proven biological effects: antibacterial, antiviral and antifungal effects, and some have antitumor properties. Thus, the prospects for prevention and treatment of many infectious diseases lie in the new possibilities for influencing mucosal immunity.

1. Afanasiev S.S., Aleshkin V.A., Voropaeva E.A., Afanasiev M.S., Slobodenyuk V.V., Karaulov A.V. Open cavity microbiocenosis and mucosal immunity. Effektivnaja farmakoterapija. 2013;27:6-11. (In Russ).

2. Klimov V.V. Mucosal immune system El. access. http://ssmu.immunology.sibhost.ru/IM/MALT.pdf Viewed 27.01.2018. (In Russ).

3. Kozlov I.G. Microbiota, mucosal immunity and antibiotics: subtleties of interaction. RMZh. 2018;8(I):19-27. (In Russ).

4. New in the physiology of mucosal immunity. Red. A.V. Karaulov, V.A. Aleshkin, S.S. Afanasiev, Yu.V. Nesvizhsky. Perm State Medical University named after I.M. Sechenov. М., 2015. 168 p. (In Russ).

5. Ruane D., Brane L., Reis B.S., Cheong C., Poles J., Do Y., Zhu H. et al. Lung dendritic cells induce migration of protec-tive T cells to the gastrointestinal tract. J Exp Med. 2013 Aug 26;210(9):1871-88. doi: 10.1084/jem.20122762. Epub 2013 Aug 19.

6. Eksteen B., Grant A.J., Miles A., Curbishley S.M., Lalor P.F., Hubscher S.G. et al. Hepatic endothelial CCL25 mediates the recruitment of CCR9 + guthoming lymphocytes to the liver in primary sclerosing cholangitis. J Exp Med. 2004;200:1511–7.

7. Campbell D.J., Butcher E.C. Rapid acquisition of tissue-specific homing phenotypes by CD4(+) T cells activated in cutaneous or mucosal lymphoid tissues. J Exp Med. 2002;195:135–41.

8. Liu Y., Wang X.Y., Yang X., Jing S., Li Z., Gao S. Lung and intestine: a specific link in an ulcerative colitis rat model. Gastroenterol Res Practice. 2013:124530.

9. Kunkel E.J., Kim C.H., Lazarus N.H., Vierra M.A., Soler D., Bowman E.P., Butcher E.C. CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells. J Clin Invest. 2003;111:1001–10.

10. Tsyvkina A.A., Luss L.V., Tsarev S.V. Mucosal immunity for upper respiratory tract pathology. Ross. allergolog. zhurnal. 2011;2:22-26. (In Russ).

11. Schuijt T.J., Lankelma J.M., Scicluna B.P. et al. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut. 2015. doi: 10.1136/gutjnl-2015-309728.

12. Samuelson D.R., Welsh D.A., Shellito J.E. Regulation of lung immunity and host defense by the intestinal microbiota. Frontiers Microbiol. 2015;6:1085.

13. Bienenstock J., McDermott M., Befus D., O’Neill M. A common mucosal immunologic system involving the bronchus, breast a nd bowel. Adv. Exp. Med. Biol. 1978;107:53–59.

14. Tulic M.K., Piche T., Verhasselt V. Lung–gut crosstalk: evidence, mechanisms and implications for the mucosal inflammatory diseases. Clin Exp Allergy. 2016 Apr;46(4):519-28. doi: 10.1111/cea.12723.

15. Zuercher A.W., Jiang H.Q., Thurnheer M.C., Cuff C.F., Cebra J.J. Distinct mechanisms for cross-protection of the upper versus lower respiratory tract through intestinal priming. J Immunol. 2002 October 1;169(7):3920-3925. doi: https://doi.org/10.4049/jimmunol.169.7.3920.

16. Fireman Z., Osipov A., Kivity S., Kopelman Y., Sternberg A., Lazarov E. et al. The use of induced sputum in the assessment of pulmonary involvement in Crohn’s disease. Am J Gastroenterol. 2000;95:730–734.

17. Tkhakushinova N.H. Clinical and epidemiological peculiarities of acute intestinal infections of viral and combined etiology in children in Krasnodar region. Jepidemiologija i infekcionnye bolezni. Aktual’nye voprosy. 2016;6:29-35. (In Russ).

18. Podkolzin A.T. Epidemiological and clinical characteristics of acute intestinal infections of viral etiology in the Russian Federation. Abstract diss. of doctor of medical sciences. М., 2015. 46 p. (In Russ).

19. Belyaev D.L., Dolgina E.N., Babayants. A.A. Participation of chronic mixedinfections with herpes viruses in the formation of severe mixed-infection syndrome of microbialviral etiology. Ross. allergolog. zhurnal. 2008;1(1):41-42. (In Russ).

20. Belan Yu.B., Polyanskaya N.A., Lobova E.F. Catamnestic observation of children with a mixed-variant of rotavirus infection. Aktual’na іnfektologіja. 2015;4:70-75. (In Russ).

21. Yushchuk N.D., Martynov Yu.V., Kukhtevich E.V., Grishina Yu.Yu. Epidemiology of infectious diseases. Textbook. M.: GEOTAR-Media, 2014. 495 p. (In Russ).

22. Golubev A.O. Clinical and immunological peculiarities of combined salmonellosis in children and immunotherapy of postinfectious bacteria carriage. Abstract diss. of candidate of medical sciences М. 2013. 22 p. (In Russ).

23. Shkarin V.V., Sergeeva A.V. Epidemiological and clinical features of combined respiratory infections in children. Detskie infekcii. 2017;16(1):51-56. (In Russ).

24. Liu Y.J. Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med. 2006;203:269-73. doi: 10.1084/jem.20051745.

25. Ichinohe T., Pang I.K., Kumamoto Y., Peaper D.R., Ho J.H., Murray T.S., Iwasaki A. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5354-9. doi: 10.1073/pnas.1019378108. Epub 2011 Mar 14.

26. Zhang Z., Hener P., Frossard N. Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma. PNAS. 2009;106:1536–41.

27. Hayitov R.M. Immunology. M.: GEOTAR-Media, 2013. 521 p. (In Russ).

28. Potta J., Mahlakoiv T., Mordstein M. IFN-λ determines the intestinal epithelial antiviral host defense. PNAS. 2011;108(19):7944-7949.

29. Izvin A. I., Kataeva L. V. Microbial landscape of the upper respiratory tract mucous membrane in normal and pathological conditions. Vestnik otorinolaringologii. 2009;2:65-68. (In Russ).

30. Aleshkin V.A., Afanasiev S.S., Karaulov A.V. Microbiocenosis and human health. Moscow: Dynasty, 2015. 548 с. (In Russ).

31. Andrianova E.N., Snegireva N.Yu., Ryvkin A.I. Disbiosis of the upper respiratory tract and changes in the functional state of respiratory organs in frequently ill children. Pediatrija. 2009;2:35-39. (In Russ).

32. Bulatova E.M., Bogdanova N.M., Lobanova E.A., Gabrusskaya T.V. Probiotics: clinical and nutritional aspects of application. Pediatrija. 2010;89(3):84–90. (In Russ).

33. West C.E., Renz H., Jenmalm M.C., Kozyrskyj A.L., Allen K.J., Vuillermin P., Prescott S.L. The gut microbiota and inflammatory non-communicable diseases: associations and potentials for gut microbiota therapies. J Allergy Clin Immunol. 2015 Jan;135(1):313; quiz 14. doi: 10.1016/j.jaci.2014.11.012.

34. Marsland B.J., Salami O. Microbiome influences on allergy in mice and humans. Curr Opin Immunol. 2015 Oct;36:94-100. doi: 10.1016/j.coi.2015.07.005. Epub 2015 Jul 26.

35. Chen Y.S., Jan R.L., Lin Y.L., Chen H.H., Wang J.Y. Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis. Pediatr Pulmonol. 2010 Nov;45(11):1111-20. doi: 10.1002/ppul.21296.

36. Zuccotti G., Meneghin F., Aceti A. Probiotics for prevention of atopic diseases in infants: systematic review and meta-analysis. Allergy. 2015;70:1356–71.

37. Lipatov I.S., Tezikov Yu.V., Santalova G.V., Ovchinnikova M.A. Prevention of herpes recurrence in pregnant women and intrauterine infection of the fetus with simplex herpes virus. Ros. vestnik akushera-ginekologa. 2014;14(4):63-68. (In Russ).

38. Lakhtin M.V., Lakhtin V.M., Afanasyev S.S. Leсtins: in solutions and sorbed, active and latent, system and network, fluorescent and chemiluminescent, in the regulation of assemblies and degradation, synergistic and symbiotic. Zdorov’e i obrazovanie v XXI veke. 2014;16(3):64–68. (In Russ).

39. Lakhtin M.V., Lakhtin V.M., Afanasiev S.S., Aleshkin V.A. Mucosal immune system against pathogens and tumors with the participation of «Lectin probiotics Glycopolymers» system. Bjulleten’ VSNC SO RAMN. 2015;3:62–69. (In Russ).

40. Lakhtin M.V., Lakhtin V.M., Afanasiev S.S. Defensive systems cofunctioning: mucosal immunity and human complement system. Bjulleten’ VSNC SO RAMN. 2015;5(105):113-122. (In Russ).

41. Sanchez B., Gonzalez-Rodriguez I., Arboleya S., Lopez P., Suarez A., Ruas-Madiedo P. et al. The Effects of Bifidobacterium breve on Immune Mediators and Proteome of HT29. Cells Monolayers. 2015;Article ID 479140. http://dx.doi.org/10.1155/2015/479140

42. Mamchur V.I., Levkh A.E. Defensins endogenous peptides with antiinfection and antitumor properties (literature review). Tavricheskij mediko-biologicheskij vestnik. 2012;15(2):315-322. (In Russ).

43. Furci L., Sironi F., Tolazzi M., Vassena L., Lusso P. Alpha-defensins block the early steps of HIV-1 infection: interference with the binding of gp120 to CD4. Blood. 2007;109(29):2928–2935.

44. Artamonov A.Yu., Rybakina E.G., Orlov D.S., Korneva E.A. Biological activity and molecularcellular mechanisms of action of antimicrobial peptides of humans and animals. Fundament. nauka i klinich. medicina. 2014;11(1):5-25. (In Russ).

45. Wang G. Post-translational modifications of natural antimicrobial peptides and strategies for peptide engineering. Curr. Biotechnol. 2012;1(1):72–79.

46. Xu L. Antimicrobial activity and membraneactive mechanism of tryptophan zipper-like β-hairpin antimicrobial peptides. Amino Acids. 2015;47(11):2385–2397.

47. Dong N. Strand length-dependent antimicrobial activity and membrane-active mechanism of arginineand valine-rich β-hairpin-like antimicrobial peptides. Antimicrob. Agents Chemother. 2012;56(6):2994–3003.

48. Bullard R.S., Gibson W., Bose S.K., Belgrave J., Eaddy A., Wright C. et al. Functional analysis of the host defense peptide Human в Defensin-1: new insight into its potential role in cancer. Mol. Immunol. 2008;45(8):839–848.

49. Gunstone F., Harwood J., Dijkstra A. The Lipid Handbook. CRC Press, NY, 2007:134-141.

50. Panteleev P.V. Structural-functional study of antimicrobial peptides of animal origin. Abstract diss. for scientific degree candidate of chemical sciences. M., Institute of Bioorganic Chemistry named after academicians M.M. Shemyakin and Y.A. Ovchinnikov RAS. 2015. 24 p. (In Russ).

51. Budikhina A.S., Pinegin B.V. Defensins – multifunctional cations peptides of human. Immunopathology, allergology, infectology. 2008;2(1):31–40.

52. Dawson M.J., Scott R.W. New horizons for host defense peptides and lantibiotics. Curr. Opin. Pharmacol. 2012;12(5):545–550.

53. Islam M.R., Nagao J., Zendo T., Sonomoto K. Antimicrobial mechanism of lantibiotics. Biochem. Soc. Trans. 2012;40(6):1528–1533.

54. Kruszewska D., Sahl H.G., Bierbaum G., Pag U., Hynes S.O., Ljungh A. Mersacidin eradicates methicillin-resistant Staphylococcus aureus (MRSA) in a mouse rhinitis model. J. Antimicrob. Chemother. 2004;54:648–653.

55. Dijkshoorn L., Bogaards S., Nemec A. The synthetic N-terminal peptide of human lactoferrin, hLF(1–11), Is highly effective against experimental infection caused by multidrug-resistant Acinetobacter baumannii. Antimicrob. Chemother. 2004;48:4919-4921.

56. Fritsche T.R., Rhomberg P.R., Sader H.S., Jones R.N. Antimicrobial activity of omiganan pentahydrochloride tested against contemporary bacterial pathogens commonly responsible for catheterassociated infections. J Antimicrob Chemother. 2008;61(5):1092-1098. doi: 10.1093/jac/dkn074.

57. Min-Duk S., Hyung-Sik W., Ji-Hun K., Tsogbadrakh M., Lee B. Antimicrobial Peptides for Therapeutic Applications: A Review. Molecules. 2012;17(10): 12276-12286. doi:10.3390/molecules171012276.

58. Bondarenko V.M. Justification and tactics of prescribing various forms of probiotic drugs in medical practice. Farmateka. 2012;13:77–87. (In Russ).

59. Bondarenko V.M., Rybalchenko O.V. Analysis of prophylactic and therapeutic effects of probiotic drugs from the standpoint of new scientific technologies. Zhurnal mikrobiologii, jepidemiologii i immunobiologii. 2015;2:90–104. (In Russ).

60. Kornienko E.A., Droz dova S.N., Serebryanaya N.B. Probiotics as a way to increase the efficiency of Helicobacter pylori eradication in children. Farmateka. 2005;7:68–70. (In Russ).

61. Cruchet S., Furoes R., Maruy A., Hebel E., Palacios J., Medina F., Ramirez N. et al. The use of probiotics in pediatric gastroenterology: A review of literature and recommendations by Latin-American experts. Paediatr Drugs. 2015 Jun;17(3):199-216. doi: 10.1007/s40272-015-0124-6.

62. Guarino A., Ashkenazi S., Gendrel D., Lo Vecchio A., Shamir R., Szajewska H. ESPGHAN/European Pediatric Infectious Disease evidence-based guidelines for the management of acute gastroenteritis in children in Europe, update 2014. J. Pediatr. Gastroenterol. Nutr. 2014;59(1):132–152.

63. Houghteling P. D., Walker W. A. Why is initial bsterial colonization of the intestine important to infants’ and children’s health. J. Pediatr. Gasteroenterol. Nutr. 2015;60(3):294–307.

64. Ng S.C., Hart A.L., Kamm M.A. Mechanisms of action of probiotics: recent advances. Inflamm. Bowel Dis. 2009;15(2):301–312.

65. Spinler J.K., Tawelchotipatr M., Rognerud C.L., Rognerud C.L., Ching N., Somying O. Human-derived probiotic Lactobacillus reuteri demonstrate antimicrobial activities targeting diverse enteric bacterial pathogens. Anaerobe. 2008;14:166–171.

66. WGO. Probiotics and Prebiotics. World Gastroenterology Organization. 2011. http://www.worldgastroenterology.org

67. Albers R., Antoine J. Bourdet-Sicard R. et al. Markers to measure immunomodulation in human nutrition intervention studies. Br. J. Nutr. 2005;94:452–481.

68. Oberhelman R. A placebo6controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. J. Pediatr. 1999;134:15–20.

69. Hatakka K., Savilahti E., Ponka A. et al. Effect of long term consumption of probiotic milk on infections in children attending day care cente rs: double blind, randomized trial. B.M.J. 2001;322:1351–1367.

70. Szajewska H., Kotovska M., Mrukowicz J. et al. Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants. J. Pediatr. 2001;138:361–365.

71. Kekkonen R., Vasankari T., Vuorimaa T. et al. The effect of probi6 otic on respiratory infection and gastrointestinal symptoms during training in marathon runners. Int. J. Sport. Nutr. Exerc. Metab. 2007;17:352–363.

72. Scalabrin D.M., Harris C., Johnston W.H. Longterm safety assessment in children who received hydrolyzed protein formula with Lactobacillus rhamnosus GG: a 5-year follow-up. Eur J Pediatr. 2017;176:217–224.

73. Hojsak I., Abdovic S., Szajewska H., Milosevic M., Krznaric Z., Kolacek S. Lactobacillus GG in the Prevention of Nosocomial Gastrointestinal and Respiratory Tract Infections. Pediatrics. 2010;125:E1171-E1177.

74. McFarland L.V., Goh S. Preventing Pediatric Antibiotic-Associated Diarrhea and Clostridium difficile Infections with Probiotics: A meta-analysis. World J. Meta-Anal. 2013;1:102–120.

75. Kalliomaki M., Salminen S., Poussa T. et al. Probiotics and prevention of atopic disease: 46year follow6up of a randomized placebo6 controlled trial. Lancet. 2003;361(9372):1869–1871.

76. Myllyluoma E. LGG and immune response. Helsinki: Valio Ltd., 2008.

77. Saxelin M. LGG – Summation: Lactobacillus GG and its health effects. Helsinki: Valio Lt., 2002. 60 p.

78. Saavedra J.M., Long term consumption of infants’ formulas containing live probiotic bacteria: tolerance and safety. Am. J. Clin. Nutr. 2004;79:261–267.

79. Isolauri E., Suomalainen H. Probiotics: effects on immunity. Am. J. Clin. Nutr. 2001;73:444–450.

80. Guandolini S. Lactobacillus GG administered in oral rehidratation solution to children with acute diarrhea. J.P.G.N. 2000;30:54–60.

81. Vanderhoof J.A., Whitney D.B., Antonson D.L. et al. Lactobacillus GG in the prevention of antibiotic associated diarrhea in children. J. Pediatr. 1999;135:564–568.