Hostname: page-component-76fb5796d-zzh7m Total loading time: 0 Render date: 2024-04-25T11:17:11.181Z Has data issue: false hasContentIssue false
  • English
  • Français

Toxocara canis infection worsens the course of experimental autoimmune encephalomyelitis in mice

Published online by Cambridge University Press:  02 September 2022

Jan Novák Open the ORCID record for Jan Novák [Opens in a new window] ,
Tomáš Macháček Open the ORCID record for Tomáš Macháček [Opens in a new window] ,
Martin Majer ,
Marie Kostelanská ,
Kateřina Skulinová ,
Viktor Černý ,
Libuše Kolářová ,
Jiří Hrdý  and
Petr Horák
Jan Novák*
Affiliation:
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 7, 128 00, Praha 2, Czechia
Tomáš Macháček
Affiliation:
Department of Parasitology, Faculty of Science, Charles University, Viničná 7, 128 44, Praha 2, Czechia
Martin Majer
Affiliation:
Department of Parasitology, Faculty of Science, Charles University, Viničná 7, 128 44, Praha 2, Czechia
Marie Kostelanská
Affiliation:
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 7, 128 00, Praha 2, Czechia
Kateřina Skulinová
Affiliation:
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 7, 128 00, Praha 2, Czechia Department of Parasitology, Faculty of Science, Charles University, Viničná 7, 128 44, Praha 2, Czechia
Viktor Černý
Affiliation:
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 7, 128 00, Praha 2, Czechia
Libuše Kolářová
Affiliation:
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 7, 128 00, Praha 2, Czechia National Reference Laboratory for Tissue Helminthoses, General University Hospital in Prague, Studničkova 7, 128 00, Praha 2, Czechia
Jiří Hrdý
Affiliation:
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 7, 128 00, Praha 2, Czechia
Petr Horák
Affiliation:
Department of Parasitology, Faculty of Science, Charles University, Viničná 7, 128 44, Praha 2, Czechia
*
Author for correspondence: Jan Novák, E-mail: jan.novak2@lf1.cuni.cz
Get access Rights & Permissions [Opens in a new window]

Abstract

Toxocara canis, a gastrointestinal parasite of canids, is also highly prevalent in many paratenic hosts, such as mice and humans. As with many other helminths, the infection is associated with immunomodulatory effects, which could affect other inflammatory conditions including autoimmune and allergic diseases. Here, we investigated the effect of T. canis infection on the course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Mice infected with 2 doses of 100 T. canis L3 larvae 5 weeks prior to EAE induction (the Tc+EAE group) showed higher EAE clinical scores and greater weight loss compared to the non-infected group with induced EAE (the EAE group). Elevated concentrations of all measured serum cytokines (IL-1α, IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) were observed in the Tc+EAE group compared to the EAE group. In the CNS, the similar number of regulatory T cells (Tregs; CD4+FoxP3+Helios+) but their decreased proportion from total CD4+ cells was found in the Tc+EAE group compared to the EAE group. This could indicate that the group Tc+EAE harboured significantly more CD4+ T cells of non-Treg phenotype within the affected CNS. Altogether, our results demonstrate that infection of mice with T. canis worsens the course of subsequently induced EAE. Further studies are, therefore, urgently needed to reveal the underlying pathological mechanisms and to investigate possible risks for the human population, in which exposure to T. canis is frequent.

Keywords

EAEexperimental autoimmune encephalomyelitishelminthMOGmultiple sclerosisToxocara canis
Type
Research Article
Information
Parasitology , Volume 149 , Issue 13 , November 2022 , pp. 1720 - 1728
Check for updates
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bing, SJ, Ha, D, Ahn, G, Cho, J, Kim, A, Park, SK, Yu, HS and Jee, Y (2015) Galectin isolated from parasite inhibits remission of experimental autoimmune encephalomyelitis by up-regulating autoantibody. Clinical and Experimental Immunology 180, 419–431.CrossRefGoogle ScholarPubMed
Bittner, S, Afzali, AM, Wiendl, H and Meuth, SG (2014) Myelin oligodendrocyte glycoprotein (MOG(35–55)) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Jove-Journal of Visualized Experiments 86, e51275. doi: 10.3791/51275.CrossRefGoogle Scholar
Bowman, DD, Mikagrieve, M and Grieve, RB (1987) Circulating excretory-secretory antigen levels and specific antibody-responses in mice infected with Toxocara-canis. American Journal of Tropical Medicine and Hygiene 36, 75–82.CrossRefGoogle ScholarPubMed
Charabati, M, Donkers, SJ, Kirkland, MC and Osborne, LC (2020) A critical analysis of helminth immunotherapy in multiple sclerosis. Multiple Sclerosis Journal 26, 1448–1458.CrossRefGoogle ScholarPubMed
Chiuso-Minicucci, F, Van, DB, Zorzella-Pezavento, SFG, Peres, RS, Ishikawa, LLW, Rosa, LC, Franca, TGD, Turato, WM, Amarante, AFT and Sartori, A (2011) Experimental autoimmune encephalomyelitis evolution was not modified by multiple infections with Strongyloides venezuelensis. Parasite Immunology 33, 303–308.CrossRefGoogle Scholar
Dargahi, N, Katsara, M, Tselios, T, Androutsou, ME, de Courten, M, Matsoukas, J and Apostolopoulos, V (2017) Multiple sclerosis: immunopathology and treatment update. Brain Sciences 7, 78. doi: 10.3390/brainsci7070078.CrossRefGoogle Scholar
Desavigny, DH, Voller, A and Woodruff, AW (1979) Toxocariasis – serological diagnosis by enzyme immunoassay. Journal of Clinical Pathology 32, 284–288.CrossRefGoogle Scholar
Ditgen, D, Anandarajah, EM, Meissner, KA, Brattig, N, Wrenger, C and Liebau, E (2014) Harnessing the helminth secretome for therapeutic immunomodulators. Biomed Research International 2014, 964350. doi: 10.1155/2014/964350.CrossRefGoogle ScholarPubMed
Donskow-Lysoniewska, K, Krawczak, K and Doligalska, M (2012) Heligmosomoides polygyrus: EAE remission is correlated with different systemic cytokine profiles provoked by L4 and adult nematodes. Experimental Parasitology 132, 243–248.CrossRefGoogle ScholarPubMed
Donskow-Lysoniewska, K, Krawczak, K, Bocian, K and Doligalska, M (2018) The effects of intestinal nematode L4 stage on mouse experimental autoimmune encephalomyelitis. Archivum Immunologiae Et Therapiae Experimentalis 66, 231–243.CrossRefGoogle ScholarPubMed
Doonan, J, Thomas, D, Wong, MH, Ramage, HJ, Al-Riyami, L, Lumb, FE, Bell, KS, Fairlie-Clarke, KJ, Suckling, CJ, Michelsen, KS, Jiang, HR, Cooke, A, Harnett, MM and Harnett, W (2018) Failure of the anti-inflammatory ParasiticWorm product ES-62 to provide protection in mouse models of type I diabetes, multiple sclerosis, and inflammatory bowel disease. Molecules 23. doi: 10.3390/molecules23102669.CrossRefGoogle ScholarPubMed
Fan, CK, Holland, CV, Loxton, K and Barghouth, U (2015) Cerebral toxocariasis: silent progression to neurodegenerative disorders?. Clinical Microbiology Reviews 28, 663–686.CrossRefGoogle ScholarPubMed
Finlay, CM, Stefanska, AM, Walsh, KP, Kelly, PJ, Boon, L, Lavelle, EC, Walsh, PT and Mills, KHG (2016) Helminth products protect against autoimmunity via innate type 2 cytokines IL-5 and IL-33, which promote eosinophilia. Journal of Immunology 196, 703–714.CrossRefGoogle ScholarPubMed
Fonseca, GRE, dos Santos, SV, Chieffi, PP, de Paula, FM, Gryschek, RCB and Lescano, SAZ (2017) Experimental toxocariasis in BALB/c mice: relationship between parasite inoculum and the IgG immune response. Memorias Do Instituto Oswaldo Cruz 112, 382–386.CrossRefGoogle ScholarPubMed
Genain, CP, Abel, K, Belmar, N, Villinger, F, Rosenberg, DP, Linington, C, Raine, CS and Hauser, SL (1996) Late complications of immune deviation therapy in a nonhuman primate. Science 274, 2054–2057.CrossRefGoogle Scholar
Glickman, LT and Schantz, PM (1981) Epidemiology and pathogenesis of zoonotic toxocariasis. Epidemiologic Reviews 3, 230–250.CrossRefGoogle ScholarPubMed
Gruden-Movsesijan, A, Ilic, N, Mostarica-Stojkovic, M, Stosic-Grujicic, S, Milic, M and Sofronic-Milosavljevic, L (2010) Mechanisms of modulation of experimental autoimmune encephalomyelitis by chronic Trichinella spiralis infection in Dark Agouti rats. Parasite Immunology 32, 450–459.CrossRefGoogle ScholarPubMed
Hamilton, CM, Stafford, P, Pinelli, E and Holland, CV (2006) A murine model for cerebral toxocariasis: characterization of host susceptibility and behaviour. Parasitology 132, 791–801.CrossRefGoogle ScholarPubMed
Hauser, SL, Kappos, L, Montalban, X, Craveiro, L, Chognot, C, Hughes, R, Koendgen, H, Pasquarelli, N, Pradhan, A, Prajapati, K and Wolinsky, JS (2021) Safety of ocrelizumab in patients with relapsing and primary progressive multiple sclerosis. Neurology 97, E1546–E1559.CrossRefGoogle ScholarPubMed
Holland, CV (2017) Knowledge gaps in the epidemiology of Toxocara: the enigma remains. Parasitology 144, 81–94.CrossRefGoogle ScholarPubMed
Holland, CV and Cox, DM (2001) Toxocara in the mouse: a model for parasite-altered host behaviour? Journal of Helminthology 75, 125–135.Google Scholar
Jahan-Abad, AJ, Karima, S, Shateri, S, Baram, SM, Rajaei, S, Morteza-Zadeh, P, Borhani-Haghighi, M, Salari, AA, Nikzamir, A and Gorji, A (2020) Serum pro-inflammatory and anti-inflammatory cytokines and the pathogenesis of experimental autoimmune encephalomyelitis. Neuropathology 40, 84–92.CrossRefGoogle ScholarPubMed
Janecek, E, Beineke, A, Schnieder, T and Strube, C (2014) Neurotoxocarosis: marked preference of Toxocara canis for the cerebrum and T-cati for the cerebellum in the paratenic model host mouse. Parasites and Vectors 7, 194. doi: 10.1186/1756-3305-7-194.CrossRefGoogle ScholarPubMed
Janecek, E, Waindok, P, Bankstahl, M and Strube, C (2017) Abnormal neurobehaviour and impaired memory function as a consequence of Toxocara canis – as well as Toxocara cati-induced neurotoxocarosis. PLoS Neglected Tropical Diseases 11, 0005594. doi: 10.1371/journal.pntd.0005594.CrossRefGoogle ScholarPubMed
Kim, JY, Cho, MK, Choi, SH, Lee, KH, Ahn, SC, Kim, DH and Yu, HS (2010) Inhibition of dextran sulfate sodium (DSS)-induced intestinal inflammation via enhanced IL-10 and TGF-beta production by galectin-9 homologues isolated from intestinal parasites. Molecular and Biochemical Parasitology 174, 53–61.CrossRefGoogle ScholarPubMed
Kuijk, LM, Klaver, EJ, Kooij, G, van der Pol, SMA, Heijnen, P, Bruijns, SCM, Kringel, H, Pinelli, E, Kraal, G, de Vries, HE, Dijkstra, CD, Bouma, G and van Die, I (2012) Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation. Molecular Immunology 51, 210–218.CrossRefGoogle ScholarPubMed
La Flamme, AC, Ruddenklau, K and Backstrom, BT (2003) Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infection and Immunity 71, 4996–5004.CrossRefGoogle ScholarPubMed
Loukas, A, Maizels, RM and Hotez, PJ (2021) The yin and yang of human soil-transmitted helminth infections. International Journal for Parasitology 51, 1243–1253.CrossRefGoogle ScholarPubMed
Lund, ME, Greer, J, Dixit, A, Alvarado, R, McCauley-Winter, P, To, J, Tanaka, A, Hutchinson, AT, Robinson, MW, Simpson, AM, O'Brien, BA, Dalton, JP and Donnelly, S (2016) A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of type 1 diabetes and multiple sclerosis. Scientific Reports 6, 37789. doi: 10.1038/srep37789.CrossRefGoogle ScholarPubMed
Ma, GX, Holland, CV, Wang, T, Hofmann, A, Fan, CK, Maizels, RM, Hotez, PJ and Gasser, RB (2018) Human toxocariasis. Lancet Infectious Diseases 18, E14–E24.CrossRefGoogle ScholarPubMed
Ma, GX, Rostami, A, Wang, T, Hofmann, A, Hotez, PJ and Gasser, RB (2020). Global and regional seroprevalence estimates for human toxocariasis: a call for action. In Bowman, DD (ed.), Advances in Parasitology: Toxocara and Toxocariasis, vol. 109. London, UK: Elsevier Ltd., pp. 275–290.CrossRefGoogle ScholarPubMed
Maizels, RM (2020) Regulation of immunity and allergy by helminth parasites. Allergy 75, 524–534.CrossRefGoogle ScholarPubMed
Maizels, RM and McSorley, HJ (2016) Regulation of the host immune system by helminth parasites. Journal of Allergy and Clinical Immunology 138, 666–675.CrossRefGoogle ScholarPubMed
Novák, J, Panská, L, Macháček, T, Kolářová, L and Horák, (2017) Humoral response of mice infected with Toxocara canis following different infection schemes. Acta Parasitologica 62, 823–835.CrossRefGoogle ScholarPubMed
Ohtani, S, Kohyama, K and Matsumoto, Y (2011) Autoantibodies recognizing native MOG are closely associated with active demyelination but not with neuroinflammation in chronic EAE. Neuropathology 31, 101–111.CrossRefGoogle Scholar
Ollero, MD, Fenoy, S, Cuellar, C, Guillen, JL and del Aguila, C (2008) Experimental toxocariosis in BALB/c mice: effect of the inoculation dose on brain and eye involvement. Acta Tropica 105, 124–130.CrossRefGoogle ScholarPubMed
Peon, AN, Ledesma-Soto, Y, Olguin, JE, Bautista-Donis, M, Sciutto, E and Terrazas, LI (2017) Helminth products potently modulate experimental autoimmune encephalomyelitis by downregulating neuroinflammation and promoting a suppressive microenvironment. Mediators of Inflammation 2017, 8494572. doi: 10.1155/2017/8494572.CrossRefGoogle ScholarPubMed
Pino, PA and Cardona, AE (2011) Isolation of brain and spinal cord mononuclear cells using Percoll gradients. Jove-Journal of Visualized Experiments 48, 2348. doi: 10.3791/2348.Google Scholar
Radovic, I, Gruden-Movsesijan, A, Ilic, N, Cvetkovic, J, Mojsilovic, S, Devic, M and Sofronic-Milosavljevic, L (2015) Immunomodulatory effects of Trichinella spiralis-derived excretory-secretory antigens. Immunologic Research 61, 312–325.CrossRefGoogle ScholarPubMed
Reyes, JL, Espinoza-Jimenez, AF, Gonzalez, MI, Verdin, L and Terrazas, LI (2011) Taenia crassiceps infection abrogates experimental autoimmune encephalomyelitis. Cellular Immunology 267, 77–87.CrossRefGoogle ScholarPubMed
Rubinsky-Elefant, G, Hirata, CE, Yamamoto, JH and Ferreira, MU (2010) Human toxocariasis: diagnosis, worldwide seroprevalences and clinical expression of the systemic and ocular forms. Annals of Tropical Medicine and Parasitology 104, 3–23.CrossRefGoogle ScholarPubMed
Sewell, D, Qing, Z, Reinke, E, Elliot, D, Weinstock, J, Sandor, M and Fabry, Z (2003) Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. International Immunology 15, 59–69.CrossRefGoogle ScholarPubMed
Smallwood, TB, Giacomin, PR, Loukas, A, Mulvenna, JP, Clark, RJ and Miles, JJ (2017) Helminth immunomodulation in autoimmune disease. Frontiers in Immunology 8, 453. doi: 10.3389/fimmu.2017.00453.CrossRefGoogle ScholarPubMed
Sofronic-Milosavljevic, L, Radovic, I, Ilic, N, Majstorovic, I, Cvetkovic, J and Gruden-Movsesijan, A (2013) Application of dendritic cells stimulated with Trichinella spiralis excretory-secretory antigens alleviates experimental autoimmune encephalomyelitis. Medical Microbiology and Immunology 202, 239–249.CrossRefGoogle ScholarPubMed
Strube, C, Heuer, L and Janecek, E (2013) Toxocara spp. infections in paratenic hosts. Veterinary Parasitology 193, 375–389.CrossRefGoogle ScholarPubMed
Strube, C, Waindok, P, Raulf, MK and Springer, A (2020 a) Toxocara-induced neural larva migrans (neurotoxocarosis) in rodent model hosts. In Bowman, DD (ed.), Advances in Parasitology: Toxocara and Toxocariasis, vol. 109. London, UK: Elsevier Ltd., pp. 189–218.CrossRefGoogle Scholar
Strube, C, Raulf, MK, Springer, A, Waindok, P and Auer, H (2020 b) Seroprevalence of human toxocarosis in Europe: a review and meta-analysis. In Bowman, DD (ed.), Advances in Parasitology: Toxocara and Toxocariasis, vol. 109. Elsevier Ltd, pp. 375–418.CrossRefGoogle Scholar
Terrazas, C, Ruiz-Rosado, JD, Amici, SA, Jablonski, KA, Martinez-Saucedo, D, Webb, LM, Cortado, H, Robledo-Avila, F, Oghumu, S, Satoskar, AR, Rodriguez-Sosa, M, Terrazas, LI, Guerau-de-Arellano, M and Partida-Sanchez, S (2017) Helminth-induced Ly6C(hi) monocyte-derived alternatively activated macrophages suppress experimental autoimmune encephalomyelitis. Scientific Reports 7, 40814. doi: 10.1038/srep40814.CrossRefGoogle Scholar
Tran, GT, Wilcox, PL, Dent, LA, Robinson, CM, Carter, N, Verma, ND, Hall, BM and Hodgkinson, SJ (2017) Interleukin-5 mediates parasite-induced protection against experimental autoimmune encephalomyelitis: association with induction of antigen-specific CD4(+) CD25(+) T regulatory cells. Frontiers in Immunology 8, 1453. doi: 10.3389/fimmu.2017.01453.CrossRefGoogle ScholarPubMed
Waindok, P and Strube, C (2019) Neuroinvasion of Toxocara canis – and T. cati-larvae mediates dynamic changes in brain cytokine and chemokine profile. Journal of Neuroinflammation 16, 147. doi: 10.1186/s12974-019-1537-x.CrossRefGoogle Scholar
Walsh, KP, Brady, MT, Finlay, CM, Boon, L and Mills, KHG (2009) Infection with a helminth parasite attenuates autoimmunity through TGF-beta-mediated suppression of Th17 and Th1 responses. Journal of Immunology 183, 1577–1586.CrossRefGoogle ScholarPubMed
White, MPJ, Johnston, CJC, Grainger, JR, Konkel, JE, O'connor, RA, Anderton, SM and Maizels, RM (2020) The Helminth Parasite Heligmosomoides polygyrus Attenuates EAE in an IL-4R alpha-Dependent Manner. Frontiers in Immunology 11, 1830. doi: 10.3389/fimmu.2020.01830.CrossRefGoogle Scholar
Wilson, MS, Taylor, MD, O'Gorman, MT, Balic, A, Barr, TA, Filbey, K, Anderton, SM and Maizels, RM (2010) Helminth-induced CD19(+)CD23(hi) B cells modulate experimental allergic and autoimmune inflammation. European Journal of Immunology 40, 1682–1696.CrossRefGoogle Scholar
Wu, ZL, Nagano, I, Asano, K and Takahashi, Y (2010) Infection of non-encapsulated species of Trichinella ameliorates experimental autoimmune encephalomyelitis involving suppression of Th17 and Th1 response. Parasitology Research 107, 1173–1188.CrossRefGoogle ScholarPubMed
Zheng, XP, Hu, XQ, Zhou, GY, Lu, ZQ, Qiu, W, Bao, H and Dai, YQ (2008) Soluble egg antigen from Schistosoma japonicum modulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response. Journal of Neuroimmunology 194, 107–114.CrossRefGoogle ScholarPubMed
Zhu, B, Trikudanathan, S, Zozulya, AL, Sandoval-Garcia, C, Kennedy, JK, Atochina, O, Norberg, T, Castagner, B, Seeberger, P, Fabry, Z, Harn, D, Khoury, SJ and Guleria, I (2012) Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis. Clinical Immunology 142, 351–361.CrossRefGoogle ScholarPubMed
Supplementary material: Image

Novák et al. supplementary material

Novák et al. supplementary material

Download Novák et al. supplementary material(Image)
Image 851.9 KB