Immunomodulatory effect of hemozoin from Opisthorchis felineus and its participation in reducing allergic inflammation through activation of the inflammasome

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Molecules of the excretory-secretory product arising as a result of co-evolution of a host and a parasite are able to inhibit the type 2 immune response, while activating the type 1 and the type 17 responses. The ability to alter the immune response can be used to inhibit inflammation in allergic diseases. In this regard, a search for helminth-associated molecules both with an immunomodulatory effect and immunogenicity and low toxicity is represented as a topical task.

Hemozoin being a dark brown insoluble biocrystal is an excretory product of a number of hematophagous parasites (Schistosoma mansoni, Plasmodium falciparum and Opisthorchis felineus). This substance as a compound of parasitic origin with explicit immunomodulatory properties has prospects for deep research.

Lots of relevant literature has been studied carefully before developing a concept about Opisthorchis felineus hemozoin and its unique properties.

Thus, the current review presents an analysis of the accumulated data regarding the effect of Opisthorchis felineus trematode on the host immune system. Also the data on the immunomodulatory effect of hemozoin of various origins is analyzed. The current knowledge on the immune mechanisms of inflammasome activation and the possible role of hemozoin in reducing allergic inflammation through this mechanism is represented in this article.

According to the systemized research results the excretory-secretory molecule of the liver fluke is a product of parasitic origin with an explicit immunomodulatory effect which is promising for prospective scientific study. Opisthorchis felineus extract increases the expression of T-regulatory cells and inhibits the Th2-immune response.

Hemozoin produced by Opisthorchis felineus, like one produced by Plasmodium falciparum, may be involved in reducing the activity of allergic inflammation through activation of the inflammasome. Comprehension of the mechanism of how hemozoin interacts with the host immune system can be applied for correction of conditions associated with Th2-polarization of the immune response, which primarily include atopic diseases.

Studying the mechanism of inflammation will help by the search for a biological target to create a vaccine to prevent the spread of atopic diseases, including bronchial asthma.

About the authors

Anasyasiay P. Melenteva

Siberian State Medical University

Author for correspondence.
Email: anastasiaymelenteva@gmail.com
ORCID iD: 0009-0009-5600-5760
Russian Federation, Tomsk

Tamara A. Parshutkina

Siberian State Medical University

Email: tamara.parshutkina@gmail.com
ORCID iD: 0009-0008-3948-3608
Russian Federation, Tomsk

Ludmila M. Ogorodova

Siberian State Medical University

Email: edu@tomsk.gov.ru
ORCID iD: 0000-0002-2962-1076

MD, Dr. Sci. (Med.), Professor, corresponding member of the Russian Academy of Sciences

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

MD, Dr. Sci. (Med.)

Russian Federation, Tomsk

References

  1. Vasileiadou S, Ekerljung L, Bjerg A, Goksör E. Asthma increased in young adults from 2008–2016 despite stable allergic rhinitis and reduced smoking. PLoS One. 2021;16(6):e0253322. EDN: VTRWEP doi: 10.1371/journal.pone.0253322
  2. Windsor JW, Kaplan GG. Evolving epidemiology of IBD. Curr Gastroenterol Rep. 2019;21(8):40. EDN: KHUTQP doi: 10.1007/s11894-019-0705-6
  3. Biagioni B, Vitiello G, Bormioli S, et al. Migrants and allergy: A new view of the atopic march. Eur Ann Allergy Clin Immunol. 2019;51(3):100–114. doi: 10.23822/EurAnnACI.1764-1489.96
  4. Khosravi M, Mirsamadi ES, Mirjalali H, Zali MR. Isolation and functions of extracellular vesicles derived from parasites: The promise of a new era in immunotherapy, vaccination, and diagnosis. Int J Nanomedicine. 2020;(15):2957–2969. EDN: MJUUBP doi: 10.2147/IJN.S250993
  5. Lothstein KE, Gause WC. Mining helminths for novel therapeutics. Trends Mol Med. 2021;27(4):345–364. doi: 10.1016/j.molmed.2020.12.010
  6. Wenjie S, Ning X, Xuelin W, et al. Helminth therapy for immune-mediated inflammatory diseases: Current and future perspectives. J Inflammat Res. 2022;(15):475–491. EDN: HLEQUG doi: 10.2147/JIR.S348079
  7. Hendrik JP, van der Zande, Zawistowska-Deniziak A, Guigas B. Immune regulation of metabolic homeostasis by helminths and their molecules. Trends Parasitol. 2019;35(10):795–808. doi: 10.1016/j.pt.2019.07.014
  8. Wu Z, Wang L, Tang Y, Sun X. Parasite-derived proteins for the treatment of allergies and autoimmune diseases. Front Microbiol. 2017;(8):2164. doi: 10.3389/fmicb.2017.02164
  9. Maruszewska-Cheruiyot M, Szewczak L, Krawczak-Wójcik K, et al. The production of excretory-secretory molecules from Heligmosomoides polygyrus bakeri fourth stage larvae varies between mixed and single sex cultures. Parasit Vectors. 2021;14(1):1–10. EDN: NOZQIY doi: 10.1186/s13071-021-04613-9
  10. Zakeri A, Hansen EP, Andersen SD, et al. Immunomodulation by helminths: Intracellular pathways and extracellular vesicles. Front Immunol. 2018;(9):2349. doi: 10.3389/fimmu.2018.02349
  11. Pershina AG, Saltykova IV, Ivanov VV, et al. Hemozoin "knobs" in O. felineus infected liver. Parasit Vectors. 2015;(8):459. EDN: UZZGJT doi: 10.1186/s13071-015-1061-5
  12. Lvova M, Zhukova M, Kiseleva E, et al. Hemozoin is a product of heme detoxification in the gut of the most medically important species of the family Opisthorchiidae. Int J Parasitol. 2016;46(3):147–156. doi: 10.1016/j.ijpara.2015.12.003
  13. Evdoklmova ТА, Ogorodova LM. Influence of chronic opistorchis invasion upon immune response and clinical presentations of pediatric bronchial asthma. Pediatriya: zhurnal imeni G.N. Speranskogo. 2005;84(6):12–17. EDN: HSTFKZ
  14. Ogorodova LM, Freidin MB, Sazonov AE, et al. Opistorchis felineus invasion influence on immunity in bronchial asthma. Bulletin Siberian Med. 2010;9(3):85–90. EDN: MSMIQD doi: 10.20538/1682-0363-2010-3-85-90.
  15. Saltykova IV, Ittiprasert W, Nevskaya KV, et al. Hemozoin from the liver fluke, O. felineus, modulates dendritic cell responses in bronchial asthma patients. Front Vet Sci. 2019;(6):332. EDN: PDCHOC doi: 10.3389/fvets.2019.00332
  16. Ogorodova LM, Freidin MB, Sazonov AE, et al. Study of occurrence and correlation between allergic diseases and opisthorchiasis in the population of the Tomsk Region. Bulletin Siberian Med. 2006;5(4):48–51. EDN: HVQRGH doi: 10.20538/1682-0363-2006-4-48-51
  17. Ogorodova LM, Freidin MB, Sazonov AE, et al. A pilot screening of prevalence of atopic states and opisthorchosis and their relationship in people of Tomsk Oblast. Parasitol Res. 2007;101(4):1165–1168. doi: 10.1007/s00436-007-0588-6
  18. Fedorova OS, Janse JJ, Ogorodova LM, et al. O. felineus negatively associates with skin test reactivity in Russia-EuroPrevall-International Cooperation study. Allergy. 2017;72(7):1096–1104. EDN: XMXPYP doi: 10.1111/all.13120
  19. Fyodorova OS. Food allergy prevalence in children of opisthorchiasis world region. Bulletin Siberian Med. 2010;9(5):102–107. EDN: MVJFYX doi: 10.20538/1682-0363-2010-5-102-107
  20. Saltykova IV, Ogorodova LM, Bragina EY, et al. O. felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma. Acta Trop. 2014;(139):53–56. EDN: UEMZWL doi: 10.1016/j.actatropica.2014.07.004
  21. Kirillova NA, Deyev IA, Kremer YE, et al. T-regulatory cells subpopulation in bronchial asthma and heterogeneous phenotypes of chronic obstructive pulmonary disease. Bulletin Siberian Med. 2011;10(1):48–54. EDN: MKRKHY doi: 10.20538/1682-0363-2011-1-48-54
  22. Gonsorunova DS, Ogorodova LM, Fyodorova OS, et al. Т-regulatory cells in atopic dermatitis immune response. Bulletin Siberian Med. 2011;10(4):82–88. EDN: OFNNVD doi: 10.20538/1682-0363-2011-4-82-88
  23. Kremer EÉ, Ogorodova LM, Kirillova NA, et al. [Immunophenotypic characteristic of dendritic cells in bronchial asthma in conditions of extract O. felineus in vitro. (In Russ)]. Annals Russ Academ Med Sci. 2013;(5):66–70. EDN: QCUWIL doi: 10.15690/vramn.v68i5.665
  24. Pack AD, Schwartzhoff PV, Zacharias ZR, et al. Hemozoin-mediated inflammasome activation limits long-lived anti-malarial immunity. Cell Rep. 2021;36(8):109586. doi: 10.1016/j.celrep.2021.109586
  25. Fontana MF, Saphire EO, Pepper M. Plasmodium infection disrupts the T follicular helper cell response to heterologous immunization. Elife. 2023(12):e83330. doi: 10.7554/eLife.83330
  26. Surette FA, Guthmiller JJ, Li L, et al. Extrafollicular CD4 T cell-derived IL-10 functions rapidly and transiently to support anti-Plasmodium humoral immunity. PLoS Pathog. 2021;17(2):e1009288. doi: 10.1371/journal.ppat.1009288
  27. Chen MM, Shi L, Sullivan DJ. Haemoproteus and schistosoma synthesize heme polymers similar to plasmodium hemozoin and beta-hematin. Mol Biochem Parasitol. 2001;113(1):1–8. doi: 10.1016/s0166-6851(00)00365-0
  28. Hoang AN, Ncokazi KK, de Villiers KA, et al. Crystallization of synthetic haemozoin (beta-haematin) nucleated at the surface of lipid particles. Dalton Trans. 2010;39(5):1235–1244. doi: 10.1039/b914359a
  29. Coronado LM, Nadovich CT, Spadafora C. Malarial hemozoin: From target to tool. Biochim Biophys Acta. 2014;1840(6):2032–2041. doi: 10.1016/j.bbagen.2014.02.009
  30. Xiao SH, Sun J. Schistosoma hemozoin and its possible roles. Int J Parasitol. 2017;47(4):171–183. doi: 10.1016/j.ijpara.2016.10.005
  31. Egan TJ. Haemozoin formation. Mol Biochem Parasitol. 2008;157(2):127–36. doi: 10.1016/j.molbiopara.2007.11.005
  32. Dostert C, Guarda G, Romero JF, et al. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS One. 2009;4(8):e6510. doi: 10.1371/journal.pone.0006510
  33. Uraki R, Das SC, Hatta M, et al. Hemozoin as a novel adjuvant for inactivated whole virion influenza vaccine. Vaccine. 2014;32(41):5295–5300. doi: 10.1016/j.vaccine.2014.07.079
  34. Griffith JW, Sun T, McIntosh MT, Bucala R. Pure Hemozoin is inflammatory in vivo and activates the NALP3 inflammasome via release of uric acid. J Immunol. 2009;183(8):5208–5220. doi: 10.4049/jimmunol.0713552
  35. Jaramillo M, Gowda DC, Radzioch D, Olivier M. Hemozoin increases IFN-gamma-inducible macrophage nitric oxide generation through extracellular signal-regulated kinase- and NF-kappa B-dependent pathways. J Immunol. 2003;171(8):4243–4253. doi: 10.4049/jimmunol.171.8.4243
  36. Urban BC, Todryk S. Malaria pigment paralyzes dendritic cells. J Biol. 2006;5(2):4. doi: 10.1186/jbiol37
  37. Jiang Y, Xue X, Chen X, et al. Hemozoin from Schistosoma japonicum does not affect murine myeloid dendritic cell function. Parasitol Res. 2010;106(3):653–659. doi: 10.1007/s00436-009-1717-1
  38. Truscott M, Evans DA, Gunn M, Hoffmann KF. Schistosoma mansoni hemozoin modulates alternative activation of macrophages via specific suppression of retnla expression and secretion. Infect Immun. 2013;81(1):133–142. doi: 10.1128/IAI.00701-12
  39. Lee MS, Igari Y, Tsukui T, et al. Current status of synthetic hemozoin adjuvant: A preliminary safety evaluation. Vaccine. 2016;34(18):2055–2061. doi: 10.1016/j.vaccine.2016.02.064
  40. Bobade D, Khandare AV, Deval M, et al. Hemozoin-induced activation of human monocytes toward M2-like phenotype is partially reversed by antimalarial drugs-chloroquine and artemisinin. Microbiologyopen. 2019;8(3):e00651. doi: 10.1002/mbo3.651.
  41. Maknitikul S, Luplertlop N, Chaisri U, et al. Featured article: Immunomodulatory effect of hemozoin on pneumocyte apoptosis via CARD9 pathway, a possibly retarding pulmonary resolution. Exp Biol Med (Maywood). 2018;243(5):395–407. doi: 10.1177/1535370218757458
  42. Keller CC, Yamo O, Ouma C, et al. Acquisition of hemozoin by monocytes down-regulates interleukin-12 p40 (IL-12p40) transcripts and circulating IL-12p70 through an IL-10-dependent mechanism: In vivo and in vitro findings in severe malarial anemia. Infect Immun. 2006;74(9):5249–5260. doi: 10.1128/IAI.00843-06
  43. Sherry BA, Alava G, Tracey KJ, et al. Malaria-specific metabolite hemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered thermoregulation in vivo. J Inflamm. 1995;45(2):85–96.
  44. Ranjan R, Karpurapu M, Rani A, et al. Hemozoin regulates inos expression by modulating the transcription factor NF-ΚB in macrophages. Biochem Mol Biol J. 2016;2(2):10. doi: 10.21767/2471-8084.100019
  45. Dostert C, Guarda G, Romero JF, et al. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS One. 2009;4(8):e6510. doi: 10.1371/journal.pone.0006510
  46. Perkins DJ, Moore JM, Otieno J, et al. In vivo acquisition of hemozoin by placental blood mononuclear cells suppresses PGE2, TNF-alpha, and IL-10. Biochem Biophys Res Commun. 2003;311(4):839–846. doi: 10.1016/j.bbrc.2003.10.073
  47. Shio MT, Eisenbarth SC, Savaria M, et al. Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases. PLoS Pathog. 2009;5(8):e1000559. doi: 10.1371/journal.ppat.1000559
  48. Saltykova IV, Ittiprasert W, Nevskaya KV, et al. Hemozoin from the liver fluke, O. felineus, modulates dendritic cell responses in bronchial asthma patients. Front Vet Sci. 2019;(6):332. doi: 10.3389/fvets.2019.00332
  49. Schwarzer E, Skorokhod OA, Barrera V, Arese P. Hemozoin and the human monocyte: A brief review of their interactions. Parassitologia. 2008;50(1-2):143–145.
  50. Deroost K, Tyberghein A, Lays N, et al. Hemozoin induces lung inflammation and correlates with malaria-associated acute respiratory distress syndrome. Am J Respir Cell Mol Biol. 2013;48(5):589–600. doi: 10.1165/rcmb.2012-0450OC
  51. Skorokhod OA, Alessio M, Mordmüller B, et al. Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: A peroxisome proliferator-activated receptor-gamma-mediated effect. J Immunol. 2004;173(6):4066–4074. doi: 10.4049/jimmunol.173.6.4066
  52. Schwarzer E, Alessio M, Ulliers D, Arese P. Phagocytosis of the malarial pigment, hemozoin, impairs expression of major histocompatibility complex class II antigen, CD54, and CD11c in human monocytes. Infect Immun. 1998;66(4):1601–1606. doi: 10.1128/IAI.66.4.1601-1606.1998
  53. Waseem S, Ur-Rehman K, Kumar R, Mahmood T. Hemozoin enhances maturation of murine bone marrow derived macrophages and myeloid dendritic cells. Iran J Immunol. 2016;13(1):1–8.
  54. Cambos M, Bazinet S, Abed E, et al. The IL-12p70/IL-10 interplay is differentially regulated by free heme and hemozoin in murine bone-marrow-derived macrophages. Int J Parasitol. 2010;40(9):1003–1012. doi: 10.1016/j.ijpara.2010.02.007
  55. Shi W, Xu N, Wang X, et al. Helminth therapy for immune-mediated inflammatory diseases: Current and future perspectives. J Inflamm Res. 2022;(15):475–491. doi: 10.2147/JIR.S348079
  56. Liu JY, Li LY, Yang XZ, et al. Adoptive transfer of dendritic cells isolated from helminth-infected mice enhanced T regulatory cell responses in airway allergic inflammation. Parasite Immunol. 2011;(33):525–534. doi: 10.1111/j.1365-3024.2011.01308.x
  57. Coronado LM, Nadovich CT, Spadafora C. Malarial hemozoin: From target to tool. Biochim Biophys Acta. 2014;1840(6):2032–2041. doi: 10.1016/j.bbagen.2014.02.009
  58. Broz P, Dixit VM. Inflammasomes: Mechanism of assembly, regulation and signalling. Nat Rev Immunol. 2016;16(7):407–420. doi: 10.1038/nri.2016.58
  59. Toldo S, Mauro AG, Cutter Z, Abbate A. Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2018;315(6):H1553–H1568. doi: 10.1152/ajpheart.00158.2018
  60. De Queiroz GA, da Silva RR, de Pires AO, et al. New variants in NLRP3 inflammasome genes increase risk for asthma and Blomia tropicalis-induced allergy in a Brazilian population. Cytokine X. 2020;2(3):100032. doi: 10.1016/j.cytox.2020.100032
  61. Madouri F, Guillou N, Fauconnier L, et al. Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation. J Mol Cell Biol. 2015;7(4):351–365. doi: 10.1093/jmcb/mjv012
  62. Préfontaine D, Lajoie-Kadoch S, Foley S, et al. Increased expression of IL-33 in severe asthma: Evidence of expression by airway smooth muscle cells. J Immunol. 2009;183(8):5094–5103. doi: 10.4049/jimmunol.0802387
  63. Faustino LD, Griffith JW, Rahimi RA, et al. Luster interleukin-33 activates regulatory T cells to suppress innate γδ T cell responses in the lung. Nat Immunol. 2020;21(11):1371–1383. doi: 10.1038/s41590-020-0785-3

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Supplement 1. Classification of molecules of helminth origin (adapted from S. Wenjie et al. [55])
Download (11KB)
Indexing metadata

Copyright (c) 2024 Pharmarus Print Media

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies