Original Article

Marshallagia marshalli Antigen Strengthens Dendritic Cell Mediated T Lymphocyte Regulation on Asthmatic Patients

Abstract

Background: The current study was conducted to investigate the antigenic effect of Marshallagia marshalli on the treatment of asthma by measuring the secreted inhibitory cytokine.

Methods: Case patients and controls were selected from clinics in Mashhad, Khorasan Razavi Province, Northeastern Iran in 2017-18. In this experimental study, peripheral blood mononuclear cells (PBMCs) were isolated from 15 patients with asthma and 10 healthy controls and were cultured. PBMCs were then converted to tolerogenic DCs through exposure to GM-CSF, IL-4 and M. marshalli antigen. Then, tolerogenic DCs were exposed to autologous T cells for five days and finally, the level of secreted TGF-β1 was measured.

Results: The mean TGF-β1 level in the control and control groups was 210.2 ± 8.2 and 225.4 ± 6.1 pq/ml, respectively. The results showed that TGF-β1 levels in both groups significantly increased in both groups (P<0.001). In addition, TGF-β1 levels in the case group were significantly higher than the control group (P<0.001).

Conclusion: M. marshalli antigen increase the level of TGF-β1 and can create antigen-bearing dendritic cells and shift T lymphocytes to the regulatory type. This parasite can be used in dendritic cell therapy to control allergic diseases.

1. Lambrecht BN, Hammad H. The immunology of asthma. Nature Immunol. 2015;16(1):45.
2. Pelaia G, Vatrella A, Busceti MT, et al. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma. Mediators of inflammation. 2015;2015.
3. Rico-Rosillo G, Vega-Robledo GB, Silva-Garcia R, et al. [Epigenetics, environment and asthma]. Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993). 2014;61(2):99-109.
4. Bergmann KC. Asthma. Chem Immunol Allergy. 2014;100:69-80.
5. Cavkaytar O, Sekerel BE. Baseline management of asthma control. Allergologia Immunopathol. 2014;42(2):162-8.
6. Chung KF. Targeting the interleukin pathway in the treatment of asthma. The Lancet. 2015;386(9998):1086-96.
7. Kourie HR, Klastersky J. Immune checkpoint inhibitors side effects and management. J Immunother. 2016;8(7):799-807.
8. Fahy JV. Type 2 inflammation in asthma present in most, absent in many. Nat Rev Immunol.. 2015;15(1):57.
9. Hondowicz BD, An D, Schenkel JM, et al. Interleukin-2-dependent allergen-specific tissue-resident memory cells drive asthma. Immunity. 2016;44(1):155-66.
10. Capone M, Maggi L, Santarlasci V, et al. Chitinase 3-like-1 is produced by human Th17 cells and correlates with the level of inflammation in juvenile idiopathic arthritis patients. Clin Mol Allergy. 2016;14(1):16.
11. Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012;18(5):673.
12. Ramadani F, Upton N, Hobson P, et al. Intrinsic properties of germinal center‐derived B cells promote their enhanced class switching to IgE. Allergy. 2015;70(10):1269-77.
13. Tellier J, Shi W, Minnich M, et al. Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response. Nat immunol. 2016;17(3):323.
14. Legaki E, Gazouli M. Influence of environmental factors in the development of inflammatory bowel diseases. World J Gastrointest Pharmacol Ther. 2016;7(1):112-25.
15. Boughattas I, Hattab S, Boussetta H, et al. Impact of heavy metal contamination on oxidative stress of Eisenia andrei and bacterial community structure in Tunisian mine soil. Environ Sci Pollut Res Int. 2017;24(22):18083-95.
16. Maltman C, Donald LJ, Yurkov V. Two distinct periplasmic enzymes are responsible for tellurite/tellurate and selenite reduction by strain ER-Te-48 associated with the deep sea hydrothermal vent tube worms at the Juan de Fuca Ridge black smokers. Archives Microbiol. 2017;199(8):1113-20.
17. Santos LN, Pacheco LGC, Pinheiro CS, et al. Recombinant proteins of helminths with immunoregulatory properties and their possible therapeutic use. Acta tropica. 2017;166:202-11.
18. Jabbari Azad F, Kiaee F, Rezaei A, et al. Downregulation of immune responses in asthmatic humans by ES products of Marshallagia marshalli. Clin Respir J T. 2017;11(1):83-9.
19. Finlay CM, Walsh KP, Mills KH. Induction of regulatory cells by helminth parasites: exploitation for the treatment of inflammatory diseases. Immunol Rev. 2014;259(1):206-30.
20. van Riet E, Hartgers FC, Yazdanbakhsh M. Chronic helminth infections induce imm-unomodulation: consequences and mechanisms. Immunobiol. 2007;212(6):475-90.
21. Shirvan SP, Ebrahimby A, Dousty A, et al. Somatic extracts of Marshallagia marshalli downregulate the Th2 associated immune responses in ovalbumin-induced airway inflammation in BALB/c mice. Parasites & Vectors. 2017;10(1):233.
22. Akdis M. Immune tolerance in allergy. Current Opinion Immunol. 2009;21(6):700-7.
23. Sojka DK, Huang YH, Fowell DJ. Mechanisms of regulatory T‐cell suppression–a diverse arsenal for a moving target. Immunol. 2008;124(1):13-22.
24. Beyer M, Schultze JL. Regulatory T cells: major players in the tumor microenvironment. Curr Pharm Des. 2009;15(16):1879-92.
25. Takahashi T. Dendritic cell therapy. Nihon Rinsho. 2001;59(12):2421-6.
26. De Vleeschouwer S, Van Calenbergh F, Demaerel P, et al. Transient local response and persistent tumor control in a child with recurrent malignant glioma: treatment with combination therapy including dendritic cell therapy: case report. J Neurosurg Pediatr. 2004;100(5):492-7.
27. Hilkens C, Isaacs J. Tolerogenic dendritic cell therapy for rheumatoid arthritis: where are we now? Clin Exp Immunol. 2013;172(2):148-57.
28. McCurry KR, Colvin BL, Zahorchak AF, et al. Regulatory dendritic cell therapy in organ transplantation. Transpl Int. 2006;19(7):525-38.
29. Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol. 2005;5(4):296.
30. Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity. 2013;39(1):38-48.
31. Inaba K, Metlay JP, Crowley MT, et al. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med. 1990;172(2):631-40.
32. Lloyd CM, Hessel EM. Functions of T cells in asthma: more than just T H 2 cells. Nat Rev Immunol. 2010;10(12):838.
33. Hagel I, Cabrera M, Di Prisco MC. Helminthic Infections and Asthma: Still a Challenge for Developing Countries. Respiratory Disease and Infection-A New Insight: InTech; 2013.
34. Moradpour N, Borji H, Razmi G, et al.. Pathophysiology of Marshallagia marshalli in experimentally infected lambs. Parasitol. 2013;140(14):1762-7.
35. Shirvan SP, Borji H, Movassaghi A, et al. Anti-inflammatory potentials of excretory/secretory (ES) and somatic products of Marshallagia marshalli on allergic airway inflammation in BALB/c mice. Iran J Parasitol. 2016;11(4):515.
36. Jin Y, Wi HJ, Choi M-H, et al. Regulation of anti-inflammatory cytokines IL-10 and TGF-β in mouse dendritic cells through treatment with Clonorchis sinensis crude antigen. Exp Mol Med. 2014;46(1):e74.
37. Remoue F, To Van D, Schacht AM, et al. Gender‐dependent specific immune response during chronic human Schistosomiasis haematobia. Clin Exp Immunol. 2001;124(1):62-8.
38. Yang J, Zhao J, Yang Y, et al. Schistosoma japonicum egg antigens stimulate CD4+ CD25+ T cells and modulate airway inflammation in a murine model of asthma. Immunol. 2007;120(1):8-18.
39. Dittrich AM, Erbacher A, Specht S, et al. Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model. J Immunol. 2008;180(3):1792-9.
Files
IssueVol 15 No 1 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijpa.v15i1.2525
Keywords
Marshallagia marshalli Dendritic cells T-Lymphocytes Asthma

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
HEMATI F, MIRSADRAEI M, HEMATI M, MOHEBALIAN H, BORJI H. Marshallagia marshalli Antigen Strengthens Dendritic Cell Mediated T Lymphocyte Regulation on Asthmatic Patients. Iran J Parasitol. 2020;15(1):40-47.