Preview

Bulletin of Siberian Medicine

Advanced search

The role of the microbiota components in modification of the immune response in some cases of chronic obstructive pulmonary disease

https://doi.org/10.20538/1682-0363-2017-2-125-135

Abstract

Background. According to the World Health Organization, chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality in the world. COPD with frequent exacerbations is a most challenging variant of the disease. Currently it is not clear how respiratory microbiota can modify the immune response in this disease.

Aim. To establish the role of bacterial oligonucleotides in modification of the immune response in patients with COPD.

Materials and мethods. In accordance with the protocol of the study, 10 patients with stable COPD with frequent exacerbations and 10 patients without frequent exacerbations were included. Immature dendritic cells were obtained by culturing the monocyte fraction of the peripheral blood of patients with COPD. The cells were stimulated by addition of bacterial lipopolysaccharide and small oligodeoxynucleotides (CpG-ODN) of A or B classes. Then the immunophenotypical profile of the obtained cells was determined by flow-cytometry with the use of monoclonal antibodies to antigens CD40, CD83, CD86. To determine the antigen-presenting properties, these dendritic cells were cultivated with CD4+, and then the phenotypic profile of the obtained T-lymphocytes was evaluated by using antibodies to CD4, CD25, CD127, and CD45RO.

Results. Cultivation of stimulated dendritic cells by СpG-ODN of A class with T-cells in COPD patients without exacerbations leads to an increase of the amount of lymphocytes of CD25+CD45RO phenotype (15% increase after stimulation), in contrast to the group of patients with frequent exacerbations of COPD (p = 0,018). It may indicate inadequate control of persistent inflammation, mediated by CD25+CD45RO pool of cells in the group of COPD patients with frequent exacerbations.

Conclusion. This study demonstrated the presence of discoordination of the immune response of a bidirectional nature in patients with COPD with frequent and infrequent exacerbations. 

About the Authors

Natalia A. Kirillova
Siberian State Medical University
Russian Federation

PhD, Assistant

2, Moskow Trakt, Tomsk, 634050



Ksenia V. Nevskaya
Siberian State Medical University
Russian Federation

PhD, Junior Researcher

2, Moskow Trakt, Tomsk, 634050



Vyacheslav A. Petrov
Siberian State Medical University
Russian Federation

Junior Researcher

2, Moskow Trakt, Tomsk, 634050



Julia B. Dorofeeva
Siberian State Medical University
Russian Federation

Junior Researcher

2, Moskow Trakt, Tomsk, 634050



Sergey V. Fedosenko
Siberian State Medical University
Russian Federation

DM, Assistant

2, Moskow Trakt, Tomsk, 634050



Evgeny S. Kulikov
Siberian State Medical University
Russian Federation

DM, Head of Scientific Department, Associate Professor

2, Moskow Trakt, Tomsk, 634050



References

1. Lopez A.D., Shibuya K., Rao C., Mathers C.D., Hansell A.L., Held L.S., Schmid V., Buist S. Chronic obstructive pulmonary disease: current burden and future projections // Eur. Respir. J. 2006; 27: 397–412.

2. Mathers C.D., Loncar D. Projections of global mortality and burden of disease from 2002 to 2030 // PLoS Med. 2006; 3: e442.

3. Hurst J.R., Vestbo J., Anzueto A., Locantore N., Müllerova H., Tal-Singer R., Miller B., Lomas D.A., Agusti A., Macnee W., Calverley P., Rennard S., Wouters E.F., Wedzicha J.A.; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease // N. Engl. J. Med. 2010; 363: 1128–1138.

4. Celli B.R., Thomas N.E., Anderson J.A., Ferguson G.T., Jenkins C.R., Jones P.W., Vestbo J., Knobil K., Yates J.C., Calverley P.M. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study // Am. J. Respir. Crit. Care. Med. 2008; 178: 332–338.

5. Spencer S., Calverley P.M., Burge P.S., Jones P.W. Impact of preventing exacerbations on deterioration of health status in COPD // Eur. Respir. J. 2004; 23: 698–702.

6. Hilty M., Burke C., Pedro H., Cardenas P., Bush A., Bossley C., Davies J., Ervine A., Poulter L., Pachter L., Moffatt M.F., Cookson W.O. Disordered microbial communities in asthmatic airways // PLoS One. 2010; 5, 5(1): e8578.

7. Dy R., Sethi S. The lung microbiome and exacerbations of COPD // Curr. Opin. Pulm. Med. 2016; 22 (3): 196–202.

8. Millares L., Pérez-Brocal V., Ferrari R., Gallego M., Pomares X., García-Núñez M., Montón C., Capilla S., Monsó E., Moya A. Functional Metagenomics of the Bronchial Microbiome in COPD // PLoS One. 2015; 3, 10 (12): e0144448.

9. Häcker G., Redecke V., Häcker H. Activation of the immune system by bacterial CpG-DNA // Immunology. 2002. 105 (3): 245–251.

10. Van Pottelberge G.R., Bracke K.R., Joos G.F., Brusselle G.G. The role of dendritic cells in the pathogenesis of COPD: liaison officers in the front line // COPD. 2009; Aug., 6 (4): 284–290.

11. Agrawal D.K., Shao Z. Pathogenesis of allergic airway inflammation // Curr. Allergy Asthma Rep. 2010; 10: 39–48.

12. Idoyaga J. and Steinman R.M. SnapShot: Dendritic сells // Cell. 2011; 146: 660–660.

13. Roos-Engstrand E., Ekstrand-Hammarström B., Pourazar J., Behndig A.F., Bucht A., Blomberg A. Influence of smoking cessation on airway T-lymphocyte subsets in COPD // COPD. 2009; 6 (2): 112–120.

14. Kirillova N.A. The role of T-regulatory adhesives in chronic obstructive pulmonary disease: dissertation for the degree of candidate of medical sciences. Siberian State Medical University. Tomsk, 2011 (in Russian).

15. Shaykhiev R., Crystal R.G. Innate immunity and chronic obstructive pulmonary disease: a mini-review // Gerontology. 2013; 59 (6): 481–489.

16. Mat Z., Grensemann B., Yakin Y., Knobloch J., Koch A. Effect of lipoteichoic acid on IL-2 and IL-5 release from T lymphocytes in asthma and COPD // Int. Immunopharmacol. 2012; 13 (3): 284–291.

17. R Core Team (2014). R: A language and environment for statistical computing. R Foundation for Statistical Computing,Vienna, Austria. URL: http://www.R-project.org/

18. Knobloch J., Chikosi S.J., Yanik S., Rupp J., Jungck D., Koch A. A systemic defect in Toll-like receptor 4 signaling increases lipopolysaccharide-induced suppression of IL-2-dependent T-cell proliferation in COPD // Am. J. Physiol. Lung Cell Mol. Physiol. 2016; 310 (1): 24–39.

19. Brusselle G.G., Joos G.F., Bracke K.R. New insights into the immunology of chronic obstructive pulmonary disease // Lancet. 2011; 378: 1015–1026.

20. Tsoumakidou M., Bouloukaki I., Koutala H., Kouvidi K., Mitrouska I., Zakynthinos S., Tzanakis N., Jeffery P.K., Siafakas N.M. Decreased sputum mature dendritic cells in healthy smokers and patients with chronic obstructive pulmonary disease // Int. Arch. Allergy Immunol. 2009; 150: 389–397.

21. Rogers A.V., Adelroth E., Hattotuwa K., Dewar A., Jeffery P.K. Bronchial mucosal dendritic cells in smoker sandex – smoker swith COPD: an electron microscopic study // Thorax. 2008; 63: 108–114.

22. Zanini A., Spanevello A., Baraldo S., Majori M., Della Patrona S., Gumiero F., Aiello M., Olivieri D., Saetta M., Chetta A. Decreased maturation of dendritic cells in the central airways of COPD patients is associated with VEGF, TGF-β and vascularity // Respiration. 2014; 87: 234–242.

23. Freeman C.M., Martinez F.J., Han M.K., Ames T.M., Chensue S.W., Todt J.C., Arenberg D.A., Meldrum C.A., Getty C., McCloskey L., Curtis J.L. Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease // Am. J. Respir. Crit. Care Med. 2009; Dec. 15, 180 (12): 1179–1188.

24. Stoll P., Heinz A.S., Bratke K., Bier A., Garbe K., Kuepper M., Virchow J.C., Lommatzsch M. Impact of smoking on dendritic cell phenotypes in the airway lumen of patients with COPD // Respir Res. 2014; 15: 48.

25. Liao S.X., Ding T., Rao X.M., Sun D.S., Sun P.P., Wang Y.J., Fu D.D., Liu X.L., Ou-Yang Y. Cigarette smoke affects dendritic cell maturation in the small airways of patients with chronic obstructive pulmonary disease // Mol. Med. Rep. 2015; 11: 219–225.

26. Demedts I.K., Bracke K.R., Van Pottelberge G., Testelmans D., Verleden G.M., Vermassen F.E., Joos G.F., Brusselle G.G. Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease // Am. J. Respir. Crit. Care Med. 2007; 175: 998–1005.

27. Vassallo R.,Walters P.R., Lamont J., Kottom T.J., Yi E.S., Limper A.H. Cigarette smoke promotes dendritic cell accumulation in COPD; a lung tissue research consortium study // Respir Res. 2010; 11: 45–57.

28. Le Rouzic O., Koné B., Kluza J., Marchetti P., Hennegrave F., Olivier C., Kervoaze G., Vilain E., Mordacq C., Just N., Perez T., Bautin N., Pichavant M., Gosset P. Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response // Respir Res. 2016; 17 (1): 94.

29. McCullagh B.N., Comellas A.P., Ballas Z.K., Newell J.D. Jr., Zimmerman M.B., Azar A.E.. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD) // PLoS One. 2017; 12 (2): e0172437.

30. Bhat T.A., Panzica L., Kalathil S.G., Thanavala Y. Immune dysfunction in patients with chronic obstructive pulmonary disease // Ann. Am. Thorac. Soc. 2015; 12 (Suppl 2): S169–S175.

31. Cosio M.G., Saetta M., Agusti A. Immunologic aspects of chronic obstructive pulmonary disease // N. Engl. J. Med. 2009; 360: 2445–2454.

32. Hou J., Sun Y., Hao Y., Zhuo J., Liu X., Bai P., Han J., Zheng X., Zeng H. Imbalance between subpopulations of regulatory T-cells in COPD // Thorax. 2013; 68: 1131–1139.

33. Kalathil S.G., Lugade A.A., Pradhan V., Miller A., Parameswaran G.I., Sethi S., Thanavala Y. T-regulatory cells and programmed death 1+ T-cells contribute to effector T-cell dysfunction in patients with chronic obstructive pulmonary disease. // Am. J. Respir. Crit. Сare Med. 2014; 190: 40–50.

34. Li H., Liu Q., Jiang Y., Zhang Y., Zhang Y., Xiao W. Disruption of th17/treg balance in the sputum of patients with chronic obstructive pulmonary disease // Am. J. Med. Sci. 2015. 349: 392– 397.

35. Barceló B., Pons J., Ferrer J.M., Sauleda J., Fuster A., Agustí A.G. Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco smoking // Eur. Respir. J. 2008; 31: 555–562.

36. Cappello F., Caramori G., Campanella C., Vicari C., Gnemmi I., Zanini A., Spanevello A., Capelli A., La Rocca G., Anzalone R., Bucchieri F., D’Anna S.E., Ricciardolo F.L., Brun P., Balbi B., Carone M., Zummo G., Conway de Macario E., Macario A.J., Di Stefano A. Convergentsets of data from in vivo and in vitro methods point to an active role of Hsp 60 in chronic obstructive pulmonary disease pathogenesis // PLoS One. 2011; 6: e28200.

37. Pridgeon C., Bugeon L., Donnelly L., Straschil U., Tudhope S.J., Fenwick P., Lamb J.R., Barnes P.J., Dallman M.J. Regulation of IL-17 in chronic inflammation in the human lung // Clin. Sci. (Lond). 2011; 120: 515–524.

38. Isajevs S., Taivans I., Strazda G., Kopeika U., Bukovskis M., Gordjusina V., Kratovska A. Decreased FOXP3 expression in small airways of smokers with COPD // Eu.r Respir J. 2009; 33: 61–67.

39. Lee S.H., Goswami S., Grudo A., Song L.Z., Bandi V., Goodnight White S.,Green L., Hacken-Bitar J., Huh J., Bakaeen F., Coxson H.O., Cogswell S., Storness-Bliss C., Corry D.B., Kheradmand F. Antielastin autoimmunity in tobacco smoking-induced emphysema // Nat. Med. 2007; 13: 567–569.


Review

For citations:


Kirillova N.A., Nevskaya K.V., Petrov V.A., Dorofeeva J.B., Fedosenko S.V., Kulikov E.S. The role of the microbiota components in modification of the immune response in some cases of chronic obstructive pulmonary disease. Bulletin of Siberian Medicine. 2017;16(2):125-135. (In Russ.) https://doi.org/10.20538/1682-0363-2017-2-125-135

Views: 1051


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)