DOI QR코드

DOI QR Code

Trichinella Infection Ameliorated Vincristine-Induced Neuroinflammation in Mice

  • Jo, Young Rae (Peripheral Neuropathy Research Center, Department of Molecular Neuroscience, College of Medicine, Dong-A University) ;
  • Park, Hwan Tae (Peripheral Neuropathy Research Center, Department of Molecular Neuroscience, College of Medicine, Dong-A University) ;
  • Yu, Hak Sun (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Kong, Hyun-Hee (Department of Parasitology, College of Medicine, Dong-A University)
  • Received : 2022.07.29
  • Accepted : 2022.08.05
  • Published : 2022.08.31

Abstract

Vincristine (VCR) is a chemotherapeutic agent widely used in treatment of malignancies. However, VCR has a limitation in use since it commonly causes a painful neuropathy (VCR-induced peripheral neuropathy, VIPN). Inflammatory cytokines secreted by immune cells such as macrophages can exacerbate allodynia and hyperalgesia, because inhibiting the inflammatory response is a treatment target for VIPN. In this study, we investigated whether Trichinella spiralis, a widely studied helminth for its immunomodulatory abilities, can alleviate VCR-induced allodynia. Von Frey test showed that T. spiralis infection improved mechanical allodynia at 10 days after VCR injection. We further observed whether the difference was due to mitigated axon degeneration, but no significant difference between the groups in axonal degeneration in sciatic nerves and intra-epidermal nerve fibers was found. Conversely, we observed that number of infiltrated macrophages was decreased in the sciatic nerves of the T. spiralis infected mice. Moreover, treatment of T. spiralis excretory-secretory products caused peritoneal macrophages to secrete decreased level of IL-1β. This study suggests that T. spiralis can relieve VCR-induced mechanical allodynia by suppressing neuroinflammation and that application of controllable degree of helminth may prove beneficial for VIPN treatment.

Keywords

Acknowledgement

This study was supported by grants from the National Research Foundation of Korea (NRF; 2016R1A5A2007009). This research was supported by grant funded by the Ministry of Education (2022R11A1A01072033).

References

  1. Li GZ, Hu YH, Li DY, Zhang Y, Guo HL, Li YM, Chen F, Xu J. Vincristine-induced peripheral neuropathy: a mini-review. Neurotoxicology 2020; 81: 161-171. https://doi.org/10.1016/j.neuro.2020.10.004
  2. Ocean AJ, Vahdat LT. Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies. Support Care Cancer 2004; 12: 619-625. https://doi.org/10.1007/s00520-004-0657-7
  3. Geisler S, Doan RA, Strickland A, Huang X, Milbrandt J, DiAntonio A. Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice. Brain 2016; 139: 3092-3108. https://doi.org/10.1093/brain/aww251
  4. Montague K, Simeoli R, Valente J, Malcangio M. A novel interaction between CX3CR1 and CCR2 signalling in monocytes constitutes an underlying mechanism for persistent vincristine-induced pain. J Neuroinflam 2018; 15:101. https://doi.org/10.1186/s12974-018-1116-6
  5. Fleming JO, Weinstock JV. Clinical trials of helminth therapy in autoimmune diseases: rationale and findings. Parasite Immunol 2015; 37: 277-292. https://doi.org/10.1111/pim.12175
  6. Helmby H. Human helminth therapy to treat inflammatory disorders- where do we stand? BMC Immunol 2015; 16: 1-5. https://doi.org/10.1111/pim.12810
  7. Smallwood TB, Giacomin PR, Loukas A, Mulvenna JP, Clark RJ, Miles JJ. Helminth immunomodulation in autoimmune disease. Front Immunol 2017; 8: 453. https://doi.org/10.3389/fimmu.2017.00453
  8. Maruszewska-Cheruiyot M, Donskow-Lysoniewska K, Doligalska M. Helminth therapy: advances in the use of parasitic worms against Inflammatory Bowel Diseases and its challenges. Helminthol 2018; 55: 1-11. https://doi.org/10.1515/helm-2017-0048
  9. Shi W, Xu N, Wang X, Vallee I, Liu M, Liu X. Helminth therapy for immune-mediated inflammatory diseases: current and future perspectives. J Inflamm Res 2022; 15: 475-491. https://doi.org/10.2147/JIR.S348079
  10. Park HK, Cho MK, Choi SH, Kim YS, Yu HS. Trichinella spiralis infection reduces airway allergic inflammation in mice. Exp Parasitol 2011; 127: 539-544. https://doi.org/10.1016/j.exppara.2010
  11. Cho MK, Park MK, Kang SA, Choi SH, Ahn SC, Yu HS. Trichinella spiralis infection suppressed gut inflammation with CD4+CD25+Foxp3+ T cell recruitment. Korean J Parasitol 2012; 50: 385-390. https://doi.org/10.3347/kjp.2012.50.4.385
  12. Eissa MM, Mostafa DK, Ghazy AA, El Azzouni MZ, Boulos LM, Younis LK. Anti-arthritic activity of Schistosoma mansoni and Trichinella spiralis derived-antigens in adjuvant arthritis in rats: role of FOXP3+ treg cells. PLoS One. 2016;11: e0165916. https://doi.org/10.1371/journal.pone.0165916
  13. Gruden-Movsesijan A, Ilic N, Mostarica-Stojkovic M, Stosic-Grujicic S, Milic M, Sofronic-Milosavljevic L. Mechanisms of modulation of experimental autoimmune encephalomyelitis by chronic Trichinella spiralis infection in Dark Agouti rats. Parasite Immunol 2010; 32: 450-459. https://doi.org/10.1111/j.1365-3024.2010.01207.x
  14. Kang SA, Park MK, Park SK, Choi JH, Lee DI, Song SM, Yu HS. Adoptive transfer of Trichinella spiralis-activated macrophages can ameliorate both Th1- and Th2-activated inflammation in murine models. Sci Rep 2019; 9: 6547. https://doi.org/10.1038/s41598-019-43057-1
  15. Han C, Yu J, Zhang Z, Zhai P, Zhang Y, Meng S, Yu Y, Li X, Song M. Immunomodulatory effects of Trichinella spiralis excretory-secretory antigens on macrophages. Exp Parasitol 2019; 196: 68-72. https://doi.org/10.1016/j.exppara.2018.10.001
  16. Kuijk LM, Klaver EJ, Kooij G, van der Pol SM, Heijnen P, Bruijns SC, Kringel H, Pinelli E, Kraal G, de Vries HE, Dijkstra CD, Bouma G, van Die I. Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation. Mol Immunol 2012; 51: 210-218. https://doi.org/10.1016/j.molimm.2012.03.020
  17. Kang SA, Cho MK, Park MK, Kim DH, Hong YC, Lee YS, Cha HJ, Ock MS, Yu HS. Alteration of helper T-cell related cytokine production in splenocytes during Trichinella spiralis infection. Vet Parasitol 2012; 186: 319-327. https://doi.org/10.1016/j.vetpar.2011.12.002
  18. Old EA, Nadkarni S, Grist J, Gentry C, Bevan S, Kim KW, Mogg AJ, Perretti M, Malcangio M. Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain. J Clin Invest 2014; 124: 2023-36. https://doi.org/10.1172/JCI71389
  19. Kang SA, Choi JH, Baek KW, Lee DI, Jeong MJ, Yu HS. Trichinella spiralis infection ameliorated diet-induced obesity model in mice. Int J Parasitol 2021; 51: 63-71. https://doi.org/10.1016/j.ijpara.2020.07.012
  20. Onkoba N, Chimbari MJ, Kamau JM, Mukaratirwa S. Metabolic and adaptive immune responses induced in mice infected with tissue-dwelling nematode Trichinella zimbabwensis. Open Vet J 2016; 6: 178-184. https://doi.org/10.4314/ovj.v6i3.6
  21. Martini R, Fischer S, Lopez-Vales R, David S. Interactions between schwann cells and macrophages in injury and inherited demyelinating disease. Glia 2008; 56: 1566-1577. https://doi.org/10.1002/glia.20766
  22. Kobpornchai P, Flynn RJ, Reamtong O, Rittisoonthorn N, Kosoltanapiwat N, Boonnak K, Boonyuen U, Ampawong S, Jiratanh M, Tattiyapong M, Adisakwattana P. A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses. PLoS Negl Trop Dis. 2020; 14: e0008192. https://doi.org/10.1371/journal.pntd.0008192
  23. Ferreira SH, Lorenzetti BB, Bristow AF, Poole S. Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue. Nature 1988; 334: 698-700. https://doi.org/10.1038/334698a0
  24. Sommer C, Petrausch S, Lindenlaub T, Toyka K V. Neutralizing antibodies to interleukin 1-receptor reduce pain associated behavior in mice with experimental neuropathy. Neurosci Lett 1999; 270: 25-28. https://doi.org/10.1016/s0304-3940(99)00450-4
  25. Carmi Y, Voronov E, Dotan S, Lahat N, Rahat MA, Fogel M, Huszar M, White MR, Dinarello CA, Apte RN. The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol. 2009; 183: 4705-4714. https://doi.org/10.4049/jimmunol.0901511
  26. Perrin FE, Lacroix S, Aviles-Trigueros M, David S. Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and interleukin-1β in Wallerian degeneration. Brain 2005; 128: 854-866. https://doi.org/10.1093/brain/awh407
  27. Rayburn ER, Ezell SJ, Zhang R. Anti-Inflammatory Agents for Cancer Therapy. Mol Cell Pharmacol 2009; 1: 29-43. https://doi.org/10.4255/mcpharmacol.09.05
  28. Capo V, Despommier DD. Clinical aspects of infection with Trichinella spp. Clin Microbiol Rev 1996; 9: 47-54. https://doi.org/10.1128/CMR.9.1.47