Immunomodulatory Effects of Bacterial Lysates Combined with Bronchoalveolar Lavage on Cytokine Regulation and T-cell Responses in Pseudomonas aeruginosa–colonized Bronchiectasis
-
Shuke Rao
,
Jiashun Xu
,
Weixia Xu
,
Yingjie Chang
,
Lichong Chen
,
Weiliang Yuan
,
Jiamin Xie
,
Huafeng Li
,
Jinjian Zhang
,
Ying Xie
,
Guihua Xu
,
Chenli Xie
Abstract
We aimed to determine the impact of combined bacterial lysates (BLs) and bronchoalveolar lavage (BAL) therapy on specific immune biomarkers (interleukin [IL]-6, IL-17, CD4+, CD8+), lung function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], maximal expiratory flow at 25% of FVC [MEF25]), and clinical symptoms in bronchiectasis patients with chronic P aeruginosa colonization. Sixty-five stable bronchiectasis patients were randomized to receive BAL plus oral BLs (treatment group) or BAL alone (control group). After 3 months, IL-6 and IL-17 levels in BAL fluid and serum, peripheral blood T-lymphocyte subsets, lung function indices, clinical symptom scores (CSS), and reinfection rates were assessed. Compared with BAL alone, the combination therapy significantly reduced IL-6 and IL-17 concentrations in both BAL fluid and serum. CD4+ and CD8+ T-cell counts increased markedly in the treatment group, correlating positively with improved lung function metrics (FEV1, MEF75%, MEF50%, MEF25%, diffusion capacity). Elevated IL-6 and IL 17 were inversely correlated with pulmonary function and positively associated with symptom severity and reinfection risk. Clinically, the treatment group demonstrated improved CSS, enhanced lung function, and reduced reinfections. BLs combined with BAL exert potent immunomodulatory effects by enhancing T-cell responses and downregulating pro-inflammatory cytokines, thereby improving both immune regulation and clinical outcomes in P aeruginosa-colonized bronchiectasis. These findings suggest BLs represent a promising adjunctive immunotherapy in chronic airway infections.
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2. Chalmers JD, Chang AB, Chotirmall SH, Dhar R, Mcshane PJ. Bronchiectasis. Nat Rev Dis Primers. 2018;4(1):45.
3. Zhu D, Huang MF, Xu A, Gao X, Huang YW, Phan T, et al. Systematic transcriptome profiling of hPSC-derived osteoblasts unveils CORIN's mastery in governing osteogenesis through CEBPD modulation. J Biol Chem. 2024;300(8):107494.
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7. Hilliam Y, Moore MP, Lamont IL, Bilton D, Haworth CS, Foweraker J, et al. Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis bronchiectasis lung. Eur Respir J. 2017;49(4).
8. [Expert consensus on the diagnosis and treatment of adult bronchiectasis in china]. Zhonghua Jie He He Hu Xi Za Zhi. 2021;44(4):311-21.
9. Liu Y, Lu HW, Gu SY, Wang WW, Ge J, Jie ZJ, et al. Bronchoscopic airway clearance therapy for acute exacerbations of bronchiectasis. EBioMedicine. 2021;72:103587.
10. Suarez N, Ferrara F, Rial A, Dee V, Chabalgoity JA. Bacterial lysates as immunotherapies for respiratory infections: methods of preparation. Front Bioeng Biotechnol. 2020;8:545.
11. Zhu LL, Wang YH, Feng JH, Zhou Q. Oral bacterial lysate OM-85: advances in pharmacology and therapeutics. Drug Des Devel Ther. 2024;18:4387-4399.
12. Esposito S, Bianchini S, Bosis S, Tagliabue C, Coro I, Argentiero A, et al. A randomized, placebo-controlled, double-blinded, single-centre, phase IV trial to assess the efficacy and safety of OM-85 in children suffering from recurrent respiratory tract infections. J Transl Med. 2019;17(1):284.
13. Xie C, Wen Y, Zhao Y, Zeng S, Guo Q, Liang Q, et al. Clinical features of patients with bronchiectasis with comorbid chronic obstructive pulmonary disease in china. Med Sci Monit. 2019;25:6805-11.
14. O'Donnell AE, Barker AF, Ilowite JS, Fick RB. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase i. RhDNase study group. Chest. 1998;113(5):1329-34.
15. Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika. 1975;67(3):215-6.
16. Metersky ML, Barker AF. The pathogenesis of bronchiectasis. Clin Chest Med. 2022;43(1):35-46.
17. Mcshane PJ, Tino G. Bronchiectasis. Chest. 2019;155(4):825-33.
18. Swenson C, Schraufnagel D, Sadikot R. What is bronchiectasis? Am J Respir Crit Care Med. 2017;195(8):P15-6.
19. Radovanovic D, Santus P, Blasi F, Sotgiu G, D'Arcangelo F, Simonetta E, et al. A comprehensive approach to lung function in bronchiectasis. Respir Med. 2018;145:120-9.
20. Martinez-Garcia MA, Oscullo G, Posadas T, Zaldivar E, Villa C, Dobarganes Y, et al. Pseudomonas aeruginosa and lung function decline in patients with bronchiectasis. Clin Microbiol Infect. 2021;27(3):428-34.
21. King PT. The pathophysiology of bronchiectasis. Int J Chron Obstruct Pulmon Dis. 2009;4:411-9.
22. Barker AF. Bronchiectasis. N Engl J Med. 2002;346(18):1383-93.
23. Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. Eur Respir J. 2015;45(5):1446-62.
24. Frija-Masson J, Martin C, Regard L, Lothe MN, Touqui L, Durand A, et al. Bacteria-driven peribronchial lymphoid neogenesis in bronchiectasis and cystic fibrosis. Eur Respir J. 2017;49(4).
25. Yavasoglu I. CD4+CD8+ double-positive t-lymphocytes: pitfalls. Turk J Haematol. 2020;37(3):216-7.
26. Zander R, Schauder D, Xin G, Nguyen C, Wu X, Zajac A, et al. CD4(+) t cell help is required for the formation of a cytolytic CD8(+) t cell subset that protects against chronic infection and cancer. Immunity. 2019;51(6):1028-1042.e4.
27. Alcaraz-Serrano V, Fernandez-Barat L, Scioscia G, Llorens-Llacuna J, Gimeno-Santos E, Herrero-Cortina B, et al. Mucoid pseudomonas aeruginosa alters sputum viscoelasticity in patients with non-cystic fibrosis bronchiectasis. Respir Med. 2019;154:40-6.
28. Chai YH, Xu JF. How does pseudomonas aeruginosa affect the progression of bronchiectasis? Clin Microbiol Infect. 2020;26(3):313-8.
29. Jurkiewicz D, Zielnik-Jurkiewicz B. Bacterial lysates in the prevention of respiratory tract infections. Otolaryngol Pol. 2018;72(5):1-8.
30. Chalmers JD, Cipolla D, Thompson B, Davis AM, O'Donnell A, Tino G, et al. Changes in respiratory symptoms during 48-week treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies. Eur Respir J. 2020;56(4).
31. Xu YD, Cheng M, Shang PP, Yang YQ. Role of IL-6 in dendritic cell functions. J Leukoc Biol. 2022;111(3):695-709.
32. Lin HC, Hsieh MH, Lo YL, Huang HY, Huang SW, Huang CD, et al. IL-6 and TIMP-1 correlated to airway pathogen colonization and predict disease severity in patients with non-cystic fibrosis bronchiectasis. J Inflamm Res. 2024;17:5701-9.
33. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory t cells. Nature. 2006;441(7090):235-8.
34. Parola C, Salogni L, Vaira X, Scutera S, Somma P, Salvi V, et al. Selective activation of human dendritic cells by OM-85 through a NF-kb and MAPK dependent pathway. PLoS One. 2013;8(12):e82867.
2. Chalmers JD, Chang AB, Chotirmall SH, Dhar R, Mcshane PJ. Bronchiectasis. Nat Rev Dis Primers. 2018;4(1):45.
3. Zhu D, Huang MF, Xu A, Gao X, Huang YW, Phan T, et al. Systematic transcriptome profiling of hPSC-derived osteoblasts unveils CORIN's mastery in governing osteogenesis through CEBPD modulation. J Biol Chem. 2024;300(8):107494.
4. Vidaillac C, Chotirmall SH. Pseudomonas aeruginosa in bronchiectasis: infection, inflammation, and therapies. Expert Rev Respir Med. 2021;15(5):649-62.
5. Wang R, Ding S, Lei C, Yang D, Luo H. The contribution of pseudomonas aeruginosa infection to clinical outcomes in bronchiectasis: a prospective cohort study. Ann Med. 2021;53(1):459-69.
6. Liu Y, Du L, Zhu Y, Liu X, Zhou N, Li C, et al. A truncated mutation of MucA in pseudomonas aeruginosa from a bronchiectasis patient affects t3SS expression and inflammasome activation. Acta Biochim Biophys Sin (Shanghai). 2022;54(11):1740-47.
7. Hilliam Y, Moore MP, Lamont IL, Bilton D, Haworth CS, Foweraker J, et al. Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis bronchiectasis lung. Eur Respir J. 2017;49(4).
8. [Expert consensus on the diagnosis and treatment of adult bronchiectasis in china]. Zhonghua Jie He He Hu Xi Za Zhi. 2021;44(4):311-21.
9. Liu Y, Lu HW, Gu SY, Wang WW, Ge J, Jie ZJ, et al. Bronchoscopic airway clearance therapy for acute exacerbations of bronchiectasis. EBioMedicine. 2021;72:103587.
10. Suarez N, Ferrara F, Rial A, Dee V, Chabalgoity JA. Bacterial lysates as immunotherapies for respiratory infections: methods of preparation. Front Bioeng Biotechnol. 2020;8:545.
11. Zhu LL, Wang YH, Feng JH, Zhou Q. Oral bacterial lysate OM-85: advances in pharmacology and therapeutics. Drug Des Devel Ther. 2024;18:4387-4399.
12. Esposito S, Bianchini S, Bosis S, Tagliabue C, Coro I, Argentiero A, et al. A randomized, placebo-controlled, double-blinded, single-centre, phase IV trial to assess the efficacy and safety of OM-85 in children suffering from recurrent respiratory tract infections. J Transl Med. 2019;17(1):284.
13. Xie C, Wen Y, Zhao Y, Zeng S, Guo Q, Liang Q, et al. Clinical features of patients with bronchiectasis with comorbid chronic obstructive pulmonary disease in china. Med Sci Monit. 2019;25:6805-11.
14. O'Donnell AE, Barker AF, Ilowite JS, Fick RB. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase i. RhDNase study group. Chest. 1998;113(5):1329-34.
15. Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika. 1975;67(3):215-6.
16. Metersky ML, Barker AF. The pathogenesis of bronchiectasis. Clin Chest Med. 2022;43(1):35-46.
17. Mcshane PJ, Tino G. Bronchiectasis. Chest. 2019;155(4):825-33.
18. Swenson C, Schraufnagel D, Sadikot R. What is bronchiectasis? Am J Respir Crit Care Med. 2017;195(8):P15-6.
19. Radovanovic D, Santus P, Blasi F, Sotgiu G, D'Arcangelo F, Simonetta E, et al. A comprehensive approach to lung function in bronchiectasis. Respir Med. 2018;145:120-9.
20. Martinez-Garcia MA, Oscullo G, Posadas T, Zaldivar E, Villa C, Dobarganes Y, et al. Pseudomonas aeruginosa and lung function decline in patients with bronchiectasis. Clin Microbiol Infect. 2021;27(3):428-34.
21. King PT. The pathophysiology of bronchiectasis. Int J Chron Obstruct Pulmon Dis. 2009;4:411-9.
22. Barker AF. Bronchiectasis. N Engl J Med. 2002;346(18):1383-93.
23. Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. Eur Respir J. 2015;45(5):1446-62.
24. Frija-Masson J, Martin C, Regard L, Lothe MN, Touqui L, Durand A, et al. Bacteria-driven peribronchial lymphoid neogenesis in bronchiectasis and cystic fibrosis. Eur Respir J. 2017;49(4).
25. Yavasoglu I. CD4+CD8+ double-positive t-lymphocytes: pitfalls. Turk J Haematol. 2020;37(3):216-7.
26. Zander R, Schauder D, Xin G, Nguyen C, Wu X, Zajac A, et al. CD4(+) t cell help is required for the formation of a cytolytic CD8(+) t cell subset that protects against chronic infection and cancer. Immunity. 2019;51(6):1028-1042.e4.
27. Alcaraz-Serrano V, Fernandez-Barat L, Scioscia G, Llorens-Llacuna J, Gimeno-Santos E, Herrero-Cortina B, et al. Mucoid pseudomonas aeruginosa alters sputum viscoelasticity in patients with non-cystic fibrosis bronchiectasis. Respir Med. 2019;154:40-6.
28. Chai YH, Xu JF. How does pseudomonas aeruginosa affect the progression of bronchiectasis? Clin Microbiol Infect. 2020;26(3):313-8.
29. Jurkiewicz D, Zielnik-Jurkiewicz B. Bacterial lysates in the prevention of respiratory tract infections. Otolaryngol Pol. 2018;72(5):1-8.
30. Chalmers JD, Cipolla D, Thompson B, Davis AM, O'Donnell A, Tino G, et al. Changes in respiratory symptoms during 48-week treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies. Eur Respir J. 2020;56(4).
31. Xu YD, Cheng M, Shang PP, Yang YQ. Role of IL-6 in dendritic cell functions. J Leukoc Biol. 2022;111(3):695-709.
32. Lin HC, Hsieh MH, Lo YL, Huang HY, Huang SW, Huang CD, et al. IL-6 and TIMP-1 correlated to airway pathogen colonization and predict disease severity in patients with non-cystic fibrosis bronchiectasis. J Inflamm Res. 2024;17:5701-9.
33. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory t cells. Nature. 2006;441(7090):235-8.
34. Parola C, Salogni L, Vaira X, Scutera S, Somma P, Salvi V, et al. Selective activation of human dendritic cells by OM-85 through a NF-kb and MAPK dependent pathway. PLoS One. 2013;8(12):e82867.
| Files | ||
| Issue | Vol 25 No 4 (2026) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v25i4.21737 | |
| Keywords | ||
| Bacterial lysate Bronchiectasis Bronchoalveolar lavage Cytokines Immunomodulation Pseudomonas aeruginosa T lymphocytes | ||
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How to Cite
1.
Rao S, Xu J, Xu W, Chang Y, Chen L, Yuan W, Xie J, Li H, Zhang J, Xie Y, Xu G, Xie C. Immunomodulatory Effects of Bacterial Lysates Combined with Bronchoalveolar Lavage on Cytokine Regulation and T-cell Responses in Pseudomonas aeruginosa–colonized Bronchiectasis. Iran J Allergy Asthma Immunol. 2026;25(4):502-516.
