Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter October 15, 2017

Humoral response of mice infected with Toxocara canis following different infection schemes

Jan Novák, Lucie Panská, Tomáš Macháček, Libuše Kolářová and Petr Horák
From the journal Acta Parasitologica

Abstract

The study was focused on the dynamics of humoral response to Toxocara canis excretory-secretory antigens (TES antigens) in mice experimentally infected by T. canis L3 larvae in different ways. In particular, we compared the effect of infection with two doses of 1000 larvae vs. repeated infections with a low number of larvae (daily infection with 10 larvae and weekly infection with 100 larvae in the course of 22 weeks). In ELISA, all infections, including both schemes with lower larval doses, elicited significant antibody response. Elevated levels of total IgE and TES-antigen-specific IgM were detected on day 12 after the first infection, followed by IgG and IgG1, and later by IgG3, IgG2a and IgG2b; specific IgE response was not detected. It seems that the high levels of IgM and IgG1 represent the best markers of infection. In addition, gradual increase of IgG2a and IgG2b could help in determination of the infection course. As a byproduct of our work, a new method of infection by repeated drinking of larvae was introduced; it minimizes the pain and discomfort for the experimental mice.

  1. Disclosures: The authors declare no conflict of interest.

Acknowledgements

As for Jan Novák and Libuše Kolářová, the study was financially supported by Charles University (GAUK 32915, SVV 266508, and SVV 260369). As for Petr Horák, Tomáš Macháček and Lucie Panská, the study was financially supported by Charles University (PROGRES Q43, UNCE 204017, and SVV 244260432/2017).

References

Antolová D., Reiterová K., Stanko M., Zalesny G., Fričová J., Dvorožňáková E. 2013. Small mammals: paratenic hosts for species of Toxocara in eastern Slovakia. Journal of Helminthology, 87, 52–58. 10.1017/S0022149X11000848Search in Google Scholar PubMed

Boldiš V., Ondriska F., Špitálská E., Reiterová K. 2015. Immunodiagnostic approaches for the detection of human toxocariasis. Experimental Parasitology, 159, 252–258. 10.1016/j.exppara.2015.10.006Search in Google Scholar PubMed

Bowman D.D., Mika-Grieve M., Grieve R.B. 1987. Circulating excretory-secretory antigen levels and specific antibody response in mice infected with Toxocara canis. The American Journal of Tropical Medicine and Hygiene, 36, 75–8210.4269/ajtmh.1987.36.75Search in Google Scholar PubMed

Chan P.W., Anuar A.K., Fong M.Y., Debruyne J.A., Ibrahim J. 2001. Toxocara seroprevalence and childhood asthma among Malaysian children. Pediatrics International, 43, 350–353. 10.1046/j.1442-200X-2001-01421.xSearch in Google Scholar

Cox D.M., Holland C.V. 2001. Influence of mouse strain, infective dose and larval burden in the brain on activity in Toxocara-infected mice. Journal of Helminthology, 75, 23–3210.1079/JOH200027Search in Google Scholar PubMed

De Savigny D.H. 1975. In vitro maintenance of Toxocara canis larvae and a simple method for the production of Toxocara ES antigen for use in serodiagnostic tests for visceral larva migrans. Journal of Parasitology, 61, 781–78210.2307/3279492Search in Google Scholar

De Savigny D.H., Voller A., Woodruff A.W. 1979. Toxocariasis: serological diagnosis by enzyme immunoassay. Journal of Clinical Pathology, 32, 781–78210.1136/jcp.32.3.284Search in Google Scholar PubMed PubMed Central

Dlugosz E., Wisniewski M. 2016. Toxocara canis glycans influence antigen recognitionby mouse IgG1 and IgM antibodies. Acta Parasitologica, 61, 191–194. 10.1515/ap-2016-0026Search in Google Scholar PubMed

Fan C-K., Lin Y.H., Hung C.C., Su K.E. 2004. Larval migratory behavior of long-term-maintained Toxocara canis embryonated eggs in mice. Taiwan Veterinary Journal, 30, 99–105Search in Google Scholar

Fan C-K., Liao C-W., Cheng Y-C. 2013. Factor affecting disease manifestation of toxocariasis in humans: Genetics and environment. Veterinary Parasitology, 193, 342–352. 10.1016/j.vetpar.2012.12.030Search in Google Scholar PubMed

Fan C-K., Holland C.V., Loxton K., Barghouth U. 2015. Cerebral toxocariasis: silent progression to neurodegenerative disorders? Clinical Microbiology Reviews, 28(3), 663–686. 10.1128/CMR.00106-14Search in Google Scholar PubMed PubMed Central

Fillaux J., Mangaval F.J. 2013. Laboratory diagnosis of human toxocariasis. Veterinary Parasitology, 193, 327–336. 10.1016/j.vetpar.2012.12.028Search in Google Scholar PubMed

Fenoy S., Rodero M., Pons E., Aguila C., Cuellar C. 2008. Follow-up of antibody avidity in BALB/c mice infected with Toxocara canis. Parasitology, 135, 725–733. 10.1017/S0031182008004368Search in Google Scholar PubMed

Fonseca G.R, Santos S.V., Chieffi P.P., Paula F.M., Gryschek R.C.B., Lescano S.A.Z. 2017. Experimental toxocariasis in BALB/c mice: relationship between parasite inoculum and the IgG immune response. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, 112, 382–386. 10.1590/0074-02760160341Search in Google Scholar PubMed PubMed Central

Forstl M., Buchta V., Psohlavec J., Čermák P., Čermáková Z., Urban J., Chrzová M. 2004. Diagnostics of larval toxocariasis. Klinická mikrobiologie a infekční lêkařství, 10, 181–185Search in Google Scholar PubMed

Galvin T.J. 1964. Experimental Toxocara canis infection in chicken and pigeons. Journal of Parasitology, 50, 124–12710.2307/3276045Search in Google Scholar

Gawor J., Borecka A., Marczynska M., Dobosz S., Zarnowska-Prymek H. 2015. Risk of human toxocarosis in Poland due to Toxocara infection of dogs and cats. Acta Parasitologica, 60, 99–104. 10.1515/ap-2015-0012Search in Google Scholar PubMed

Hamilton C.M., Stafford P., Pinelli E., Holland C.V. 2006. A murine model for cerebral toxocariasis: characterization of host susceptibility and behavior. Parasitology, 132, 791–801. 10.1017/S0031182006009887Search in Google Scholar PubMed

Hamilton C.M., Brandes S., Holland C., Pinelli E. 2008. Cytokine expression in the brain of Toxocara canis-infected mice. Parasite Immunology, 30, 181–185. 10.1111/j.1365-3024.2007.01002.xSearch in Google Scholar PubMed

Havasiová-Reiterová K., Tomašovičová O., Dubinský P. 1995. Effect of various doses of infective Toxocara canis and Toxocara cati eggs on the humoral response and distribution of larvae in mice. Parasitology Research, 81, 13–1710.1007/BF00932411Search in Google Scholar PubMed

Holland C.V., Hamilton C.M. 2013. Review: The significance of cerebral toxocariasis: a model system for exploring the link between brain involvement, behavior and the immune response. Journal of Experimental Biology, 216, 78–83. 10.1242/jeb.074120Search in Google Scholar PubMed

Hubner J., Uhlíková M., Leissová M. 2001. Diagnosis of the early phase of larval toxocariasis using IgG avidity. Epidemiologie, Mikrobiologie, Imunologie, 50, 67–70Search in Google Scholar

Janecek E., Beineke A., Schnieder T., 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 & Vectors, 7, 194. 10.1186/1756-3305-7-194Search in Google Scholar PubMed PubMed Central

Jin Y., Shen C., Huh S., Sohn W.M., Choi M.H., Hong S.T. 2013. Serodiagnosis of toxocariasis by ELISA using crude antigen of Toxocara canis larvae. Korean Journal of Parasitology, 51, 433–439. 10.3347/kjp.2013.51.4.433Search in Google Scholar

Kolbeková P., Kolářová L., Větvička D., Syrůček M. 2011a. Imaging of Toxocara canis larvae labelled by CFSE in BALB/c mice. Parasitology Research, 108, 1007–1014. 10.1007/s00436-010-2145-ySearch in Google Scholar PubMed

Kolbeková P., Větvička D., Svoboda J., Skírnissson K., Leissová M., Syrůček M., Marečková H., Kolářová L. 2011b. Toxocara canis larvae reinfectiong BALB/c mice exhibit accelerated speed of migration to the CNS. Parasitology Research, 109, 1267–1278. 10.1007/s00436-011-2371-ySearch in Google Scholar

Lloyd S. 1993. Toxocara canis: the dog. In: (Eds J.W. Lewis, R.M. Maizels) Toxocara and Toxocarariasis: Clinical, epidemiological and molecular perspectives. London, Institute of Biology and the British Society for Parasitology, 11–22Search in Google Scholar

Mangaval J.F., Galindo V., Glickmann L.T., Clanet M. 1997. Human Toxocara infection of the central nervous system and neurological disorders: a case-control study. Parasitology, 115, 537–54310.1017/S0031182097001558Search in Google Scholar PubMed

Ngugi A.K., Bottomley C., Kleinschmidt I., Wagner R.G., Kakooza-Mwesige A., Ae-Ngibise K., Owusu-Agyei S., Masanja H., Kamuyu G., Odhiambo R., Chengo E., Sander J.W., Newton C.R., SEEDS Group. 2013. Prevalence of active convulsive epilepsy in sub-Saharan Africa and associated risk factors: cross-sectional and case-control studies. The Lancet Neurology, 12, 253–263. 10.1016/S1474-4422(13)70003-6Search in Google Scholar PubMed

Noordin R., Smith H.V., Mohamad S., Maizels R.M., Fong M.Y. 2005. Comparison of IgG-ELISA and IgG4-ELISA for Toxocara serodiagnosis. Acta Tropica, 93, 57–62. 10.1016/j.actatropica.2004.09.009Search in Google Scholar PubMed

Pilarczyk B., Doligalska M.J., Donskow-Schmelter K., Balicka-Ramisz A., Ramisz A. 2008. Selenium supplementation enhances the protective response to Toxocara canis larvae in mice. Parasite Immunology, 30, 394–402. 10.1111/j.1365-3024.2008.01039.xSearch in Google Scholar PubMed

Pinelli E., Withagen C., Fonville M., Verlaan A., Dormans J., van Loveren H., Nicoll G., Maizels R.M., van der Giessen J. 2005. Persistent airway hyper-responsiveness and inflammation in Toxocara canis-infected BALB/c mice. Clinical and Experimental Allergy, 35, 826–832. 10.1111/j.1365-2222.2005.02250.xSearch in Google Scholar PubMed

Pinelli E., Brandes S., Dormans J., Fonville M., Hamilton C.M., van der Giessen J. Toxocara canis: (2007): Effect of inoculum size on pulmonary pathology and cytokine expression in BALB/c mice. Experimental Parasitology, 115, 76–82. 10.1016/j.exppara.2006.06.002Search in Google Scholar PubMed

Quattrocchi G., Nicoletti A., Marin B., Bruno E., Druet-Cabanac M., Preux P.M. 2012. Toxocariasis and epilepsy: systematic review and metaanalysis. PLoS Neglected Tropical Diseases, 6, e1775. 10.1371/journal.pntd.0001775.Search in Google Scholar PubMed PubMed Central

Ranasuriya G., Mian A., Boujaoude Z., Tsigrelis C. 2014. Pulmonary toxocariasis: a case report and literature review. Infection, 42: 575–578. 10.1007/s15010-014-0587-3Search in Google Scholar PubMed

Reiterová K., Antolová D., Zalesny G., Stanko M., Špilovská S., Mošanský L. 2013. Small rodents – permanent reservoirs of toxocarosis in different habitats of Slovakia. Helminthologia, 50, 20–26. 10.2478/s11687-013-0103-9Search in Google Scholar

Roldan WH., Elefant GR., Ferreira AW. 2017. Immunoglobulin M antibodies are not specific for serodiagnosis of human toxocariasis. Parasite Immunology, 39, e12447. 10.1111/pim.12447Search in Google Scholar PubMed

Schoenardie E.R., Scaini C.J., de Costa de Avila L.F., Sperotto R.L., Borsuk S., Felicetti C.D.F., Pepe M., Berne M.E.A. 2014. Determination of avidity in BALB/c mice experimentally infected with Toxocara canis. Brazilian Journal of Veterinary Parasitology, 23(4), 403–406. 10.1590/S1984-29612014060Search in Google Scholar

Smith H.V. 1993. Antibody reactivity in toxocariasis. In: (Eds. J.W. Lewis, R.M. Maizels) Toxocara and Toxocarariasis: Clinical, epidemiological and molecular perspectives. London, Institute of Biology and the British Society for Parasitology, 91–109Search in Google Scholar

Smith H.V., Holland C.W., Taylor M., Mangaval J.F., Schantz P., Maizels R.M. 2009. How common is human toxocariasis? Towards standardizing our knowledge. Trends in Parasitology, 25, 182–188. 10.1016/j.pt.2009.01.006Search in Google Scholar PubMed

Watthanakulpanich D., Smith H.V., Hobbs G., Whalley A., Billington D. 2008. Application of Toxocara canis excretory-secretory antigens and IgG subclass antibodies (IgG1-4) in serodiagnostic assay of human toxocariasis. Acta Tropica, 106, 90–95. 10.1016/j.actatropica.2008.01.008Search in Google Scholar PubMed

Yamasaki H., Araki K., Lim P.K., Zasmy N., Mak J.W., Taib R., Aoki T. 2000. Development of a highly specific recombinant Toxocara canis second-stage larva excretory-secretory antigen for Immunodiagnosis of human toxocariasis. Journal of Clinical Microbiology, 38, 1409–141310.1128/JCM.38.4.1409-1413.2000Search in Google Scholar PubMed PubMed Central

Received: 2017-6-8
Revised: 2017-8-2
Accepted: 2017-8-11
Published Online: 2017-10-15
Published in Print: 2017-12-20

© 2017 W. Stefański Institute of Parasitology, PAS