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Organ-specific Toxocara canis larvae migration and host immune response in experimentally infected mice

  • Min Seok Kim (Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital) ;
  • Yan Jin (Department of Microbiology, Dongguk University College of Medicine) ;
  • Se Joon Woo (Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital)
  • 투고 : 2023.12.25
  • 심사 : 2024.03.19
  • 발행 : 2024.05.31

초록

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2023-00248480). The funding organization had no role in the design or conduct of this study.

참고문헌

  1. Ahn SJ, Ryoo NK, Woo SJ. Ocular toxocariasis: clinical features, diagnosis, treatment, and prevention. Asia Pac Allergy 2014;4(3):134-141. https://doi.org/10.5415/apallergy.2014.4.3.134 
  2. Kolbekova P, Kolarova L, Vetvicka D, Syrucek M. Imaging of Toxocara canis larvae labelled by CFSE in BALB/c mice. Parasitol Res 2011;108(4):1007-1014. https://doi.org/10.1007/s00436-010-2145-y 
  3. Beaver PC, Snyder CH, Carrera GM, Dent JH, Lafferty JW. Chronic eosinophilia due to visceral larva migrans; report of three cases. Pediatrics 1952;9(1):7-19. https://doi.org/10.1542/peds.9.1.7 
  4. Yang HK, Woo SJ, Hwang JM. Toxocara optic neuropathy after ingestion of raw meat products. Optom Vis Sci 2014;91(11):e267-273. https://doi.org/10.1097/OPX.0000000000000404 
  5. Strube C, Heuer L, Janecek E. Toxocara spp. infections in paratenic hosts. Vet Parasitol 2013;193(4):375-389. https://doi.org/10.1016/j.vetpar.2012.12.033 
  6. Taylor MR. The epidemiology of ocular toxocariasis. J Helminthol 2001;75(2):109-118. https://doi.org/10.1079/JOH200175 
  7. Resende NM, Gazzinelli-Guimaraes PH, Barbosa FS, Oliveira LM, Nogueira DS, et al. New insights into the immunopathology of early Toxocara canis infection in mice. Parasit Vectors 2015;8:354. https://doi.org/10.1186/s13071-015-0962-7 
  8. Kolbekova P, Vetvicka D, Svoboda J, Skirnisson K, Leissova M, et al. Toxocara canis larvae reinfecting BALB/c mice exhibit accelerated speed of migration to the host CNS. Parasitol Res 2011;109(5):1267-1278. https://doi.org/10.1007/s00436-011-2371-y 
  9. Ollero MD, Fenoy S, Cuellar C, Guillen JL, Del Aguila C. Experimental toxocariosis in BALB/c mice: effect of the inoculation dose on brain and eye involvement. Acta Trop 2008;105(2):124-130. https://doi.org/10.1016/j.actatropica.2007.11.001 
  10. Ahn SJ, Woo SJ, Hyon JY, Park KH. Cataract formation associated with ocular toxocariasis. J Cataract Refract Surg 2013;39(6):830-835. https://doi.org/10.1016/j.jcrs.2012.12.033 
  11. Bae KW, Ahn SJ, Park KH, Woo SJ. Diagnostic value of the serum anti-Toxocara IgG titer for ocular toxocariasis in patients with uveitis at a tertiary hospital in Korea. Korean J Ophthalmol 2016;30(4):258-264. https://doi.org/10.3341/kjo.2016.30.4.258 
  12. Hogan MJ, Kimura SJ, Spencer WH. Visceral larva migrans and peripheral retinitis. JAMA 1965;194(13):1345-1347. https://www.ncbi.nlm.nih.gov/pubmed/5897879 
  13. Ahn SJ, Woo SJ, Jin Y, Chang YS, Kim TW, et al. Clinical features and course of ocular toxocariasis in adults. PLoS Negl Trop Dis 2014;8(6):e2938. https://doi.org/10.1371/journal.pntd.0002938 
  14. Bashi T, Bizzaro G, Ben-Ami Shor D, Blank M, Shoenfeld Y. The mechanisms behind helminth's immunomodulation in autoimmunity. Autoimmun Rev 2015;14(2):98-104. https://doi.org/10.1016/j.autrev.2014.10.004
  15. Fan CK, Lin YH, Du WY, Su KE. Infectivity and pathogenicity of 14-month-cultured embryonated eggs of Toxocara canis in mice. Vet Parasitol 2003;113(2):145-155. https://www.ncbi.nlm.nih.gov/pubmed/12695039 
  16. Othman AA, Abdel-Aleem GA, Saied EM, Mayah WW, Elatrash AM. Biochemical and immunopathological changes in experimental neurotoxocariasis. Mol Biochem Parasitol 2010;172(1):1-8. https://doi.org/10.1016/j.molbiopara.2010.03.006 
  17. Pinelli E, Brandes S, Dormans J, Fonville M, Hamilton CM, et al. Toxocara canis: effect of inoculum size on pulmonary pathology and cytokine expression in BALB/c mice. Exp Parasitol 2007;115(1):76-82. https://doi.org/10.1016/j.exppara.2006.06.002 
  18. Jiang Z, Sun L, Ding X, Zhang T, Li S, et al. Cytokine profile in aqueous humor of patients with ocular toxocariasis. Front Med (Lausanne) 2022;9:869976. https://doi.org/10.3389/fmed.2022.869976 
  19. Pinelli E, Withagen C, Fonville M, Verlaan A, Dormans J, et al. Persistent airway hyper-responsiveness and inflammation in Toxocara canis-infected BALB/c mice. Clin Exp Allergy 2005;35(6):826-832. https://doi.org/10.1111/j.1365-2222.2005.02250.x 
  20. Hiratochi M, Takamoto M, Tatemichi S, Sugane K. Inhibition of interleukin 5 production with no influence on interleukin 4 production by an anti-allergic drug, tranilast, in Toxocara canis-infected mice. Int J Immunopharmacol 2000;22(6):463-471. https://doi.org/10.1016/s0192-0561(00)00013-8