In vitro immunomodulatory effect of Opisthorchis felineus hemozoin on dendritic cells of children with bronchial asthma

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Abstract

Predominance of the Th2 pathway was noted for adaptive immune response in atopic diseases. The Th2-type response is characterized by increased levels of IL-4, IL-5, IL-13, triggering humoral and cell-mediated immune responses associated with production of IgE, basophils, eosinophils and mast cells. Current research focuses on immunoregulatory potential of helminths and their excretory products, which have potential for the pharmaceutical industry. It is known that the parasite in host organism is able to evade the immune response and it may inhibit, alter and modify the current immune responses in the host by producing immunomodulatory substances. The excretory/secretory products resulting from the co-evolution of the host and parasite, may suppress the type 2 immune response, while activating type 1 and type 17 responses. The immunosuppressive microenvironment created by helminths may not only help them to evade the host immune response, but also prevent serious damage to the body caused by excessive inflammation. The role of liver fluke in reducing inflammation has been shown in allergic diseases. The excretory/secretory molecule of the liver fluke (hemozoin) is a promising product of parasitic origin which has a pronounced immunomodulatory properties: it is a dark brown insoluble biocrystal substance synthesized during the life of hematophagous parasites Rhodnius prolixus, Schistosoma mansoni, Plasmodium falciparum, Echinostoma trivolvis, Haemoproteus columbae, Clonorchis sinensisi and Plasmodium falciparum, Opisthorchis felineus. In this regard, the search for helminth-associated molecules exhibiting immunomodulatory effects with low toxicity and immunogenicity, seems to be an urgent task. The aim of the present study was to establish the effect of O. felineus hemozoin on the cytokine profile of dendritic cells (DCs) in patients with bronchial asthma. It was shown that a combined stimulation of DCs from examined patients with the D. pteronyssinus antigen and O. felineus hemozoin is associated with high levels of Th1 profile cytokines (IL-1β, IFNγ), as well as high activity of Treg cells (IL-10). Hence, the liver fluke hemozoin is able to change the cytokine profile of DCs in patients with bronchial asthma. This property of native hemozoin isolated from O. felineus may be further studied for correction of disorders associated with Th2 polarization of immune response which is a common feature of atopic diseases.

About the authors

Anasyasia P. Melenteva

Siberian State Medical University

Author for correspondence.
Email: anastasiaymelenteva@gmail.com
ORCID iD: 0009-0009-5600-5760
SPIN-code: 3079-5819
ResearcherId: KCY-0258-2024

Postgraduate Student, Department of Faculty Pediatrics with a Course of Childhood Diseases, Faculty of Medicine

Russian Federation, Tomsk

Maria A. Podporina

Siberian State Medical University

Email: podporina.ma@ssmu.ru
ORCID iD: 0000-0002-6398-2481
SPIN-code: 5973-7396
Scopus Author ID: 57193933503

PhD (Medicine), Assistant Professor, Department of Faculty Pediatrics with a Course of Childhood Diseases, Faculty of Medicine

Russian Federation, Tomsk

Ludmila M. Ogorodova

Siberian State Medical University

Email: edu@tomsk.gov.ru
ORCID iD: 0000-0002-2962-1076
SPIN-code: 4362-8431
Scopus Author ID: 7004641487
ResearcherId: S-5058-2016

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Honored Scientist of the Russian Federation, Professor, Department of Faculty Pediatrics with a Course of Childhood Diseases, Faculty of Medicine

Russian Federation, Tomsk

Olga S. Fedorova

Siberian State Medical University

Email: olga.sergeevna.fedorova@gmail.com
ORCID iD: 0000-0002-7130-9609
SPIN-code: 5285-4593
Scopus Author ID: 57197113883
ResearcherId: AAC-8290-2022

PhD, MD (Medicine), Professor, Vice-Rector for Research and Postgraduate Training, Head, Department of Faculty Pediatrics with a Course of Childhood Diseases, Faculty of Medicine

Russian Federation, Tomsk

References

  1. Гонсорунова Д.С., Огородова Л.М., Фёдорова О.С., Камалтынова Е.М., Белоногова Е.Г., Кремер Е.Э. Участие Т-регуляторных клеток в иммунном ответе при атопическом дерматите // Бюллетень сибирской медицины, 2011. Т. 10, № 4. С. 82-88. [Gonsorunova D.S., Ogorodova L.M., Fyodorova O.S., Kamaltynova Ye.M., Belonogova Ye.G., Kremer Ye.E. T-regulatory cells in atopic dermatitis immune response. Byulleten sibirskoy meditsiny = Bulletin of Siberian Medicine, 2011, Vol. 10, no. 4, pp. 82-88. (In Russ.)]
  2. Евдокимова Т.А., Огородова Л.М. Влияние хронической описторхозной инвазии на клиническое течение и иммунный ответ при атопической бронхиальной астме у детей. Педиатрия. Журнал им. Г.Н. Сперанского, 2005. Т. 84, № 6. С. 12-17. [Evdoklmova Т.А., Ogorodova L.M. Influence of chronic opistorchis invasion upon immune response and clinical presentations of pediatric bronchial asthma. Pediatriya. Zhurnal im. G.N. Speranskogo = Pediatrics Journal Named After G.N. Speransky, 2005, Vol. 84, no. 6, pp. 12-17. (In Russ.)]
  3. Кириллова Н.А., Деев И.А., Кремер Е.Э., Огородова Л.М., Черногорюк Г.Э. Субпопуляции Т-регуляторных клеток при бронхиальной астме и гетерогенных фенотипах хронической обструктивной болезни легких // Бюллетень сибирской медицины, 2011. Т. 10, № 1. С. 48-54. [Kirillova N.A., Deyev I.A., Kremer Y.E., Ogorodova L.M., Chernogoryuk G.E. T regulatory cells subpopulation in bronchial asthma and heterogeneous phenotypes of chronic obstructive pulmonary disease. Byulleten sibirskoy meditsiny = Bulletin of Siberian Medicine, 2011, Vol. 10, no. 1, pp. 48-54. (In Russ.)]
  4. Кремер Е.Э., Огородова Л.М., Кириллова Н.А., Хворилова К.В., Перевозчикова Т.В., Файт Е.А. Иммунофенотипическая характеристика дендритных клеток при бронхиальной астме в условиях воздействия экстрактом Opisthorchis felineus in vitro. Вестник Российской академии медицинских наук, 2013. Т. 68, № 5. С. 66-70. [Kremer E.E., Ogorodova L.M., Kirillova N.A., Chvorilova K.V., Perevozchikova T.V., Fajt E.A. Immunophenotypic сharacteristic of dendritic cells in bronchial asthma in conditions of extract Opisthorchis Felineus in vitro. Vestnik Rossiyskoy akademii meditsinskikh nauk = Annals of the Russian Academy of Medical Sciences, 2013, Vol. 68, no. 5, pp. 66-70. (In Russ.)]
  5. Огородова Л.М., Фрейдин М.Б., Сазонов А.Э., Фёдорова О.С., Деев И.А., Кремер Е.Э. Влияние инвазии Opistorchis felineus на иммунный ответ при бронхиальной астме // Бюллетень сибирской медицины, 2010. Т. 9, № 3. С. 85-90. [Ogorodova L.M., Freidin M.B., Sazonov A.E., Fyodorova O.S., Deyev I.A., Kremer Ye.E. Opistorchis felineus invasion influence on immunity in bronchial asthma. Byulleten sibirskoy meditsiny = Bulletin of Siberian Medicine, 2010, Vol. 9, no. 3, pp. 85-90. (In Russ.)]
  6. Огородова Л.М., Фрейдин М.Б., Сазонов А.Э., Федорова О.С., Гербек И.Э., Черевко Н.А., Рудко А.А., Брагина Е.Ю., Перевозчикова Т.В., Файт Е.А., Лебедева Н.Ю. Изучение распространенности аллергической патологии и описторхозной инвазии и их взаимосвязи у населения Томской области // Бюллетень сибирской медицины, 2006. Т. 5, № 4. С. 48-51. [Ogorodova L.M., Freidin M.B., Sazonov A.E., Fedorova O.S., Gerbek I.E., Cherevko N.A., Roudko A.A., Bragina Ye.Yu., Perevozchikova T.V., Fait Ye.A., Lebedeva N.Yu. Study of occurrence and correlation between allergic diseases and opisthorchiasis in the population of the Tomsk Region. Byulleten sibirskoy meditsiny = Bulletin of Siberian Medicine, 2006, Vol. 5, no. 4, pp. 48-51. (In Russ.)]
  7. Фёдорова О.С. Распространенность пищевой аллергии у детей в мировом очаге описторхоза // Бюллетень сибирской медицины, 2010. Т. 9, № 5. С. 102-107. [Fyodorova O.S. Food allergy prevalence in children of opisthorchiasis world region. Byulleten sibirskoy meditsiny = Bulletin of Siberian Medicine, 2010, Vol. 9, no. 5, pp. 102-107. (In Russ.)]
  8. Шахова Н.В., Кашинская Т.С., Камалтынова Е.М. Распространенность бронхиальной астмы и аллергических заболеваний среди детей // Аллергология и иммунология в педиатрии, 2022. № 2. С. 5-12. [Shakhova N.V., Kashinskaya T.S., Kamaltynova E.M. Prevalence of bronchial asthma and allergic diseases among children. Allergologiya i immunologiya v pediatrii = Allergology and Immunology in Pediatrics, 2022, no. 2, pp. 5-12. (In Russ.)]
  9. Amor D.A.L.M., Santos L.N., Silva E.S., de Santana M.B.R., Belitardo E.M.M.A., Sena F.A., Pontes-de-Carvalho L., Figueiredo C.A., Alcântara-Neves N.M. Toxocara canis extract fractions promote mainly the production of Th1 and regulatory cytokines by human leukocytes in vitro. Acta Trop., 2022, Vol. 234, 106579. doi: 10.1016/j.actatropica.2022.106579. PMID: 35843307.
  10. Banchereau J., Steinman R.M. Dendritic cells and the control of immunity. Nature, 1998, Vol. 392, no. 6673, pp. 245-252.
  11. Bouchery T., Kyle R., Ronchese F., Le Gros G. The differentiation of CD4(+) T-helper cell subsets in the context of helminth parasite infection. Front. Immunol., 2014, Vol. 5, 487. doi: 10.3389/fimmu.2014.00487.
  12. Faustino L.D., Griffith J.W., Rahimi R.A., Nepal K., Hamilos D.L., Cho J.L., Medoff B.D., Moon J.J., Vignali D.A.A., Luster A.D. Interleukin-33 activates regulatory T cells to suppress innate γδ T cell responses in the lung. Nat Immunol., 2020, Vol. 21, no. 11, pp. 1371-1383.
  13. Fedorova O.S., Janse J.J., Ogorodova L.M., Fedotova M.M., Achterberg R.A., Verweij J.J., Fernández-Rivas M., Versteeg S.A., Potts J., Minelli C., van Ree R., Burney P., Yazdanbakhsh M. Opisthorchis felineus negatively associates with skin test reactivity in Russia-EuroPrevall-International Cooperation study. Allergy, 2017, Vol. 72, no. 7, pp. 1096-1104.
  14. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disabilityadjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir. Med., 2017, Vol. 5, no. 9, pp. 691-706.
  15. Gour N., WillsKarp M. IL4 and IL13 signaling in allergic airway disease. Cytokine, 2015, Vol. 75, no. 1, pp. 68-78.
  16. Griffith J.W., Sun T., McIntosh M.T., Bucala R. Pure Hemozoin is inflammatory in vivo and activates the NALP3 inflammasome via release of uric acid. J. Immunol., 2009, Vol. 183, no. 8, pp. 5208-5220.
  17. Kuruvilla M.E., Vanijcharoenkarn K., Shih J.A., Lee F.E. Epidemiology and risk factors for asthma. Respir. Med., 2019, Vol. 149, pp. 16-22.
  18. Li Y., Simons F.E., HayGlass K.T. Environmental antigen-induced IL-13 responses are elevated among subjects with allergic rhinitis, are independent of IL-4, and are inhibited by endogenous IFN-gamma synthesis. J. Immunol., 1998, Vol. 161, no. 12, pp. 7007-7014.
  19. Liu J.Y., Li L.Y., Yang X.Z., Li J., Zhong G., Wang J., Li L.J., Ji B., Wu Z.Q., Liu H., Yang X., Liu P.M. Adoptive transfer of dendritic cells isolated from helminth-infected mice enhanced T regulatory cell responses in airway allergic inflammation. Parasite Immunol., 2011, Vol. 33, no. 10, pp. 525-534.
  20. Logan J., Pearson M.S., Manda S.S., Choi Y.-J., Field M., Eichenberger R.M., Mulvenna J., Nagaraj S.H., Fujiwara R.T., Gazzinelli-Guimaraes P., Bueno L., Mati V., Bethony J.M., Mitreva M., Sotillo J., Loukas A. Comprehensive analysis of the secreted proteome of adult Necator americanus hookworms. PLoS Negl. Trop. Dis., 2020, Vol. 14, no. 5, e0008237. doi: 10.1371/journal.pntd.0008237.
  21. Lothstein K.E., Gause W.C. Mining Helminths for Novel Therapeutics. Trends Mol Med., 2021, Vol. 27, no. 4, pp. 345-364.
  22. Madouri F., Guillou N., Fauconnier L., Marchiol T., Rouxel N., Chenuet P., Ledru A., Apetoh L., Ghiringhelli F., Chamaillard M., Zheng S.G., Trovero F., Quesniaux V.F.J., Ryffel B., Togbe D. Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation. J. Mol. Cell Biol., 2015, Vol. 7, no. 4, pp. 351-365.
  23. Maizels R.M. Regulation of immunity and allergy by helminth parasites. Allergy, 2020, Vol. 75, no. 3, pp. 524-534.
  24. Maruszewska-Cheruiyot M., Szewczak L., Krawczak-Wójcik K., Głaczyńska M., Donskow-Łysoniewska K. The production of excretory-secretory molecules from Heligmosomoides polygyrus bakeri fourth stage larvae varies between mixed and single sex cultures. Parasit. Vectors, 2021, Vol. 14, no. 1, 106. doi: 10.1186/s13071021046139.
  25. McSorley H.J., Chayé M.A.M., Smits H.H. Worms: Pernicious parasites or allies against allergies? Parasite Immunol., 2019, Vol. 41, no. 6, e12574. doi: 10.1111/pim.12574.
  26. Ogorodova L.M., Freidin M.B., Sazonov A.E., Fedorova O.S., Gerbek I.E., Cherevko N.A., Lebedeva N.Y. A pilot screening of prevalence of atopic states and opisthorchosis and their relationship in people of Tomsk Oblast. Parasitol. Res., 2007, Vol. 101, no. 4, pp. 1165-1168.
  27. Pershina A.G., Saltykova I.V., Ivanov V.V., Perina E.A., Demin A.M., Shevelev O.B., Buzueva I.I., Gutakovskii A.K., Vtorushin S.V., Ganebnykh I.N., Krasnov V.P., Sazonov A.E., Ogorodova L.M. Hemozoin “knobs” in Opisthorchis felineus infected liver. Parasit. Vectors., 2015, Vol. 8, 459. doi: 10.1186/s13071-015-1061-5.
  28. Préfontaine D., Lajoie-Kadoch S., Foley S., Audusseau S., Olivenstein R., Halayko A.J., Lemière C., Martin J.G., Hamid Q. Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cells. J. Immunol., 2009, Vol. 183, no. 8, pp. 5094-5103.
  29. Queiroz G.A., da Silva R.R., Pires A.O., Costa R.D.S., Alcântara-Neves N.M., da Silva T.M., Barreto M.L., Oliveira S.C., Figueirêdo C.A. New variants in NLRP3 inflammasome genes increase risk for asthma and Blomia tropicalis-induced allergy in a Brazilian population. Cytokine X, 2020, Vol. 2, no. 3, 100032. doi: 10.1016/j. cytox.2020.100032.
  30. Ryan S.M., Eichenberger R.M., Ruscher R., Giacomin P.R., Loukas A. Harnessing helminth driven immunoregulation in the search for novel therapeutic modalities. PLoS Pathog., 2020, Vol. 16, no. 5, e1008508. doi: 10.1371/journal.ppat.1008508.
  31. Saltykova I.V., Ittiprasert W., Nevskaya K.V., Dorofeeva Y.B., Kirillova N.A., Kulikov E.S., Ivanov V.V., Mann V.H., Pershina A.G., Brindley P.J. Hemozoin From the Liver Fluke, Opisthorchis felineus, Modulates Dendritic Cell Responses in Bronchial Asthma Patients. Front. Vet. Sci., 2019, Vol. 6, 332. doi: 10.3389/fvets.2019.00332.
  32. Saltykova I.V., Ogorodova L.M., Bragina E.Y., Puzyrev V.P., Freidin M.B. Opisthorchis felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma. Acta Trop., 2014, Vol. 139, pp. 53-56.
  33. Shi W., Xu N., Wang X., Vallée I., Liu M., Liu X. Helminth therapy for immune mediated inflammatory diseases: current and future perspectives. J. Inflamm. Res, 2022, Vol. 15, pp. 475-491.
  34. van der Zande H.J.P., Zawistowska-Deniziak A., Guigas B. Immune Regulation of Metabolic Homeostasis by Helminths and Their Molecules. Trends Parasitol., 2019, Vol. 35, no. 10, pp. 795-808.
  35. Zakeri A., Hansen E.P., Andersen S.D., Williams A.R., Nejsum P. Immunomodulation by helminths: intracellular pathways and extracellular vesicles. Front. Immunol., 2018, Vol. 9, 2349. doi: 10.3389/fimmu.2018.02349.

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