Hostname: page-component-8448b6f56d-m8qmq Total loading time: 0 Render date: 2024-04-24T15:40:42.331Z Has data issue: false hasContentIssue false
  • English
  • Français

Oral oocyst-induced mouse model of toxoplasmosis: effect of infection with Toxoplasma gondii strains of different genotypes, dose, and mouse strains (transgenic, out-bred, in-bred) on pathogenesis and mortality

Published online by Cambridge University Press:  14 November 2011

J. P. DUBEY ,
L. R. FERREIRA ,
J. MARTINS  and
RIMA McLEOD
J. P. DUBEY*
Affiliation:
United States Department of Agriculture, Animal Natural Resources Institute, Animal Parasitic Disease Laboratory, BARC-East, Building. 1001, Beltsville, MD 20705-2350, USA
L. R. FERREIRA
Affiliation:
United States Department of Agriculture, Animal Natural Resources Institute, Animal Parasitic Disease Laboratory, BARC-East, Building. 1001, Beltsville, MD 20705-2350, USA
J. MARTINS
Affiliation:
United States Department of Agriculture, Animal Natural Resources Institute, Animal Parasitic Disease Laboratory, BARC-East, Building. 1001, Beltsville, MD 20705-2350, USA
RIMA McLEOD
Affiliation:
Department of Ophthalmology, School of Medicine, The University of Chicago, IL 60637, USA
*
*Corresponding author: USDA, ARS, ANRI, APDL, BARC-East, Building 1001, Beltsville, MD 20705, USA. Tel: +1 301 504 8128. Fax: +1 301 504 9222. E-mail: jitender.dubey@ars.usda.gov
Get access Rights & Permissions [Opens in a new window]

Summary

Humans and other hosts acquire Toxoplasma gondii infection by ingesting tissue cysts in undercooked meat, or by food or drink contaminated with oocysts. Currently, there is no vaccine to prevent clinical disease due this parasite in humans, although, various T. gondii vaccine candidates are being developed. Mice are generally used to test the protective efficacy of vaccines because they are susceptible, reagents are available to measure immune parameters in mice, and they are easily managed in the laboratory. In the present study, pathogenesis of toxoplasmosis was studied in mice of different strains, including Human Leukocyte Antigen (HLA) transgenic mice infected with different doses of T. gondii strains of different genotypes derived from several countries. Based on many experiments, the decreasing order of infectivity and pathogenicity of oocysts was: C57BL/6 background interferon gamma gene knock out (KO), HLA-A*1101, HLA-A*0201, HLA-B*0702, Swiss Webster, C57/black, and BALB/c. Mice fed as few as 1 oocyst of Type I and several atypical strains died of acute toxoplasmosis within 21 days p.i. Some Type II, and III strains were less virulent. The model developed herein should prove to be extremely useful for testing vaccines because it is possible to accurately quantitate a challenge inoculum, test the response to different strains of T. gondii using the same preparations of oocysts which are stable for up to a year, and to have highly reproducible responses to the infection.

Keywords

Toxoplasma gondiioocystsdifferent genotypespathogenicitymouse strainsinterferon gamma knockout miceHLA transgenic mice
Type
Research Article
Information
Parasitology , Volume 139 , Issue 1 , January 2012 , pp. 1 - 13
Copyright
Copyright © Cambridge University Press 2011

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

REFERENCES

Ajzenberg, D., Bañuls, A. L., Su, C., Dumètre, A., Demar, M., Carme, B. and Dardé, M. L. (2004). Genetic diversity, clonality and sexuality in Toxoplasma gondii. International Journal for Parasitology 34, 1185–1196.CrossRefGoogle ScholarPubMed
Boyer, K., Hill, D., Mui, E., Wroblewski, K., Karrison, T., Dubey, J. P., Sautter, M., Noble, G., Withers, S., Swisher, C. N., Heydemann, P. T., Hosten, T., Babiarz, J., Lee, D., Meir, P. and McLeod, R. (2011). Unrecognized ingestion of Toxoplasma gondii oocysts causes congenital toxoplasmosis and epidemics in North America. Clinical Infectious Diseases doi:10.1093/cid/cir667CrossRefGoogle ScholarPubMed
Brown, C. R., David, C. S., Khare, S. J. and McLeod, R. (1994). Effects of human class I transgenes on Toxoplasma gondii cyst formation. Journal of Immunology 152, 4537–4541.CrossRefGoogle Scholar
Brown, C. R., Hunter, C. A., Estes, R. G., Beckmann, E., Forman, J., David, C., Remington, J. S. and McLeod, R. (1995). Definitive identification of a gene that confers resistance against Toxoplasma cyst burden and encephalitis. Immunology 85, 419–428.Google ScholarPubMed
Brown, C. R. and McLeod, R. (1990). Class I MHC genes and CD8+ T cells determine cyst number in Toxoplasma gondii infection. Journal of Immunology 145, 3438–3441.CrossRefGoogle ScholarPubMed
Buzoni-Gatel, D., Debbabi, H., Mennechet, F. J. D., Martin, V., Lepage, A. C., Schwartzman, J. D. and Kasper, L. H. (2001). Murine ileitis after intracellular parasite infection is controlled by TGF-β−producing intraepithelial lymphocytes. Gastroenterology 120, 914–924.CrossRefGoogle ScholarPubMed
Cong, H., Mui, E. J., Witola, W. H., Sidney, J., Alexander, J., Sette, A., Maewal, A. and McLeod, R. (2010). Human immunome, bioinformatic analyses using HLA supermotifs and the parasite genome, binding assays, studies of human T cell responses, and immunization of HLA-A*1101 transgenic mice including novel adjuvants provide a foundation for HLA-A03 restricted CD8+T cell epitope based, adjuvanted vaccine protective against Toxoplasma gondii. Immunome Research 6, 12–27. doi: 10.1186/1745-7580-6-12.CrossRefGoogle Scholar
Cong, H., Mui, E. J., Witola, W. H., Sidney, J., Alexander, J., Sette, A., Maewal, A. and McLeod, R. (2011). Towards an immunosense vaccine to prevent toxoplasmosis: protective Toxoplasma gondii epitopes restricted by HLA-A*0201. Vaccine 29, 754–762.CrossRefGoogle ScholarPubMed
Delhaes, L., Ajzenberg, D., Sicot, B., Bourgeot, P., Dardé, M. L., Dei-Cas, E. and Houfflin-Debarge, V. (2010). Severe congenital toxoplasmosis due to a Toxoplasma gondii strain with an atypical genotype: case report and review. Prenatal Diagnosis 30, 902–905.CrossRefGoogle ScholarPubMed
Demar, M., Ajzenberg, D., Maubon, D., Djossou, F., Panchoe, D., Punwasi, W., Valery, N., Peneau, C., Daigre, J. L., Aznar, C., Cottrelle, B., Terzan, L., Dardé, M. L. and Carme, B. (2007). Fatal outbreak of human toxoplasmosis along the Maroni River: epidemiological, clinical, and parasitological aspects. Clinical Infectious Diseases 45, e88–e95.CrossRefGoogle ScholarPubMed
Dubey, J. P. (1977). Toxoplasma, Hammondia, Besnoitia, Sarcocystis, and other tissue cyst-forming coccidia of man and animals. In Parasitic Protozoa. Vol. 3, (ed. Kreier, J. P.), pp. 101–237. Academic Press, New York, USA.Google Scholar
Dubey, J. P. (1980). Mouse pathogenicity of Toxoplasma gondii isolated from a goat. American Journal of Veterinary Research 41, 427–429.Google ScholarPubMed
Dubey, J. P. (1992). Isolation of Toxoplasma gondii from a naturally infected beef cow. Journal of Parasitology 78, 151–153.CrossRefGoogle ScholarPubMed
Dubey, J. P. (1995). Duration of immunity to shedding of Toxoplasma gondii oocysts by cats. Journal of Parasitology 81, 410–415.CrossRefGoogle ScholarPubMed
Dubey, J. P. (1997). Bradyzoite-induced murine toxoplasmosis: stage conversion, pathogenesis, and tissue cyst formation in mice fed bradyzoites of different strains of Toxoplasma gondii. Journal of Eukaryotic Microbiology 44, 592–602.CrossRefGoogle ScholarPubMed
Dubey, J. P. (2001). Oocyst shedding by cats fed isolated bradyzoites and comparison of infectivity of bradyzoites of the VEG strain Toxoplasma gondii to cats and mice. Journal of Parasitology 87, 215–219.CrossRefGoogle ScholarPubMed
Dubey, J. P. (2010). Toxoplasmosis of Animals and Humans. 2nd Edn.CRC Press. Boca Raton. FL, USA.Google Scholar
Dubey, J. P. and Desmonts, G. (1987). Serological responses of equids fed Toxoplasma gondii oocysts. Equine Veterinary Journal 19, 337–339.CrossRefGoogle ScholarPubMed
Dubey, J. P. and Frenkel, J. K. (1973). Experimental Toxoplasma infection in mice with strains producing oocysts. Journal of Parasitology 59, 505–512.CrossRefGoogle ScholarPubMed
Dubey, J. P., Graham, D. H., Blackston, C. R., Lehmann, T., Gennari, S. M., Ragozo, A. M. A., Nishi, S. M., Shen, S. K., Kwok, O. C. H., Hill, D. E. and Thulliez, P. (2002). Biological and genetic characterisation of Toxoplasma gondii isolates from chickens (Gallus domesticus) from São Paulo, Brazil: Unexpected findings. International Journal for Parasitology 32, 99–105.CrossRefGoogle Scholar
Dubey, J. P., Lunney, J. K., Shen, S. K., Kwok, O. C. H., Ashford, D. A. and Thulliez, P. (1996). Infectivity of low numbers of Toxoplasma gondii oocysts to pigs. Journal of Parasitology 82, 438–443.CrossRefGoogle ScholarPubMed
Dubey, J. P., Navarro, I. T., Sreekumar, C., Dahl, E., Freire, R. L., Kawabata, H. H., Vianna, M. C. B., Kwok, O. C. H., Shen, S. K., Thulliez, P. and Lehmann, T. (2004). Toxoplasma gondii infections in cats from Paraná, Brazil: seroprevalence, tissue distribution, and biologic and genetic characterization of isolates. Journal of Parasitology 90, 721–726.CrossRefGoogle ScholarPubMed
Dubey, J. P., Passos, L. M. F., Rajendran, ▪., Ferreira, L. R., Gennari, S. M. and Su, C. (2011 a). Isolation of viable Toxoplasma gondii from feral guinea fowl (Numida meleagris) and domestic rabbits (Oryctolagus cuniculus) from Brazil. Journal of Parasitology 97, 842–847.CrossRefGoogle ScholarPubMed
Dubey, J. P., Rajendran, C., Ferreira, L. R., Kwok, O. C. H., Sinnett, D., Majumdar, D. and Su, C. (2010). A new atypical highly mouse virulent Toxoplasma gondii genotype isolated from a wild black bear in Alaska. Journal of Parasitology 96, 713–716.CrossRefGoogle ScholarPubMed
Dubey, J. P., Rajendran, ▪., Ferreira, L. R., Martins, J., Kwok, O. C. H., Hill, D. E., Villena, I., Zhou, H., Su, C. and Jones, J. L. (2011 b). High prevalence and genotypes of Toxoplasma gondii isolated from goats from a retail meat store destined for human consumption in the USA. International Journal for Parasitology 41, 827–833.CrossRefGoogle ScholarPubMed
Dubey, J. P., Speer, C. A., Shen, S. K., Kwok, O. C. H. and Blixt, J. A. (1997). Oocyst-induced murine toxoplasmosis: life cycle, pathogenicity, and stage conversion in mice fed Toxoplasma gondii oocysts. Journal of Parasitology 83, 870–882.CrossRefGoogle ScholarPubMed
Dubey, J. P., Thulliez, P. and Powell, E. C. (1995). Toxoplasma gondii in Iowa sows: comparison of antibody titers to isolation of T. gondii by bioassays in mice and cats. Journal of Parasitology 81, 48–53.CrossRefGoogle Scholar
Dubey, J. P., Zhu, X. Q., Sundar, N., Zhang, H., Kwok, O. C. H. and Su, C. (2007). Genetic and biologic characterization of Toxoplasma gondii isolates of cats from China. Veterinary Parasitology 145, 352–356.CrossRefGoogle ScholarPubMed
Dunay, I. R., DaMatta, R. A., Fux, B., Presti, R., Greco, S., Colonna, M. and Sibley, L. D. (2008). Gr1+ (Ly6C+) inflammatory monocytes are required for mucosal resistance to the pathogen Toxoplasma gondii. Immunity 29, 306–317.CrossRefGoogle Scholar
Dunay, I. R. and Sibley, L. D. (2010). Monocytes mediate mucosal immunity to Toxoplasma gondii. Current Opinion in Immunology 22, 461–466.CrossRefGoogle ScholarPubMed
Elbez-Rubinstein, A., Ajzenberg, D., Dardé, M. L., Cohen, R., Dumètre, A., Yera, H., Gondon, E., Janaud, J. C. and Thulliez, P. (2009). Congenital toxoplasmosis and reinfection during pregnancy: case report, strain characterization, experimental model of reinfection, and review. Journal of Infectious Diseases 199, 280–285.CrossRefGoogle ScholarPubMed
Frazão-Teixeira, E., Sundar, N., Dubey, J. P., Grigg, M. E. and de Oliveira, F. C. R. (2011). Multi-locus DNA sequencing of Toxoplasma gondii isolated from Brazilian pigs identifies genetically divergent strains. Veterinary Parasitology 175, 33–39.CrossRefGoogle ScholarPubMed
Frenkel, J. K., Dubey, J. P. and Miller, N. L. (1970). Toxoplasma gondii in cats: fecal stages identified as coccidian oocysts. Science 167, 893–896.CrossRefGoogle ScholarPubMed
Grigg, M. E. and Sundar, N. (2009). Sexual recombination punctuated by outbreaks and clonal expansions predicts Toxoplasma gondii population genetics. International Journal for Parasitology 39, 925–933.CrossRefGoogle ScholarPubMed
Heimesaat, M. M., Bereswill, S., Fischer, A., Fuchs, D., Struck, D., Niebergall, J., Jahn, H. K., Dunay, I. R., Moter, A., Gescher, D. M., Schumann, R. R., Göbel, U. B. and Liesenfeld, O. (2006). Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii. Journal of Immunology 177, 8785–8795.CrossRefGoogle ScholarPubMed
Hill, D., Coss, C., Dubey, J. P., Wroblewski, K., Sautter, M., Hosten, T., Muñoz-Zanzi, C., Mui, E., Withers, S., Boyer, K., Hermes, G., Coyne, J., Jagdis, F., Burnett, A., McLeod, P., Morton, H., Robinson, D. and McLeod, R. (2011). Identification of a sporozoite-specific antigen from Toxoplasma gondii. Journal of Parasitology 97, 328–337.CrossRefGoogle ScholarPubMed
Hutchison, W. M., Dunachie, J. F. and Work, K. (1968). Brief report. The faecal transmission of Toxoplasma gondii. Acta Pathologica et Microbiologica Scandinavica 74, 462–464.CrossRefGoogle Scholar
Jamieson, S. E., de Roubaix, L. A., Cortina-Borja, M., Tan, H. K., Mui, E. J., Cordell, H. J., Kirisits, M. J., Miller, E. N., Peacock, C. S., Hargrave, A. C., Coyne, J. J., Boyer, K., Bessieres, M.-H., Buffolano, W., Ferret, N., Franck, J., Kieffer, F., Meier, P., Nowakowska, D. E., Paul, M., Peyron, F., Stray-Pedersen, B., Prusa, A. R., Thulliez, P., Wallon, M., Petersen, E., McLeod, R., Gilbert, R. E. and Blackwell, J. M. (2008). Genetic and epigenetic factors at COL2A1 and ABCA4 influence clinical outcome in congenital toxoplasmosis. PLoS ONE 3, e2285.CrossRefGoogle ScholarPubMed
Jamieson, S. E., Peixoto-Rangel, A. L., Hargrave, A. C., de Roubaix, L. A., Mui, E. J., Boulter, N. R., Miller, E. N., Fuller, S. J., Wiley, J. S., Castellucci, L., Boyer, K., Peixe, R. G., Kirisits, M. J., Elias, L. D., Coyne, J. J., Correa-Oliveira, R., Sautter, M., Smith, N. C., Lees, M. P., Swisher, C. N., Heydemann, P., Noble, A. G., Patel, D., Bardo, D., Burrowes, D., McLone, D., Roizen, N., Withers, S., Bahia-Oliveira, L. M., McLeod, R. and Blackwell, J. M. (2010). Evidence for associations between the purinergic receptor P2X7 (P2RX7) and toxoplasmosis. Genes and Immunity 11, 374–383.CrossRefGoogle ScholarPubMed
Johnson, J. J., Roberts, C. W., Pope, C., Roberts, F., Kirisits, M. J., Estes, R., Mui, E., Krieger, T., Brown, C. R., Forman, J., and McLeod, R. (2002 b). In vitro correlates of Ld-restricted resistance to toxoplasmic encephalitis and their critical dependence on parasite strain. Journal of Immunology 169, 966–973.CrossRefGoogle ScholarPubMed
Johnson, J., Suzuki, Y., Mack, D., Mui, E., Estes, R., David, C., Skamene, E., Forman, J. and McLeod, R. (2002 a). Genetic analysis of influences on survival following Toxoplasma gondii infection. International Journal for Parasitology 32, 179–185.CrossRefGoogle ScholarPubMed
Lees, M. P., Fuller, S. J., McLeod, R., Boulter, N. R., Miller, C. M., Zakrzewski, A. M., Mui, E. J., Witola, W. H., Coyne, J. J., Hargrave, A. C., Jamieson, S. E., Blackwell, J. M., Wiley, J. S. and Smith, N. C. (2010). P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages. Journal of Immunology 184, 7040–7046.CrossRefGoogle ScholarPubMed
Liesenfeld, O. (2002). Oral infection of C57BL/6 mice with Toxoplasma gondii: A new model of inflammatory bowel disease? Journal of Infectious Diseases 185 (Suppl 1), S96–S101.CrossRefGoogle ScholarPubMed
Liesenfeld, O., Kosek, J., Remington, J. S. and Suzuki, Y. (1996). Association of CD4+ T cell-dependent, interferon-γ-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. Journal of Experimental Medicine 184, 597–607.CrossRefGoogle ScholarPubMed
Lunde, M. N. and Jacobs, L. (1983). Antigenic differences between endozoites and cystozoites of Toxoplasma gondii. Journal of Parasitology 69, 806–808.CrossRefGoogle ScholarPubMed
Mack, D., Johnson, J. J., Roberts, F., Roberts, C. W., Estes, R. G., David, C., Grumet, F. C. and McLeod, R. (1999). HLA-class II genes modify outcome of Toxoplasma gondii infection. International Journal for Parasitology 29, 1351–1358.CrossRefGoogle ScholarPubMed
McLeod, R., Brown, C. and Mack, D. (1993). Immunogenetics influence outcome of Toxoplasma gondii infection. Research in Immunology 144, 61–65.CrossRefGoogle ScholarPubMed
McLeod, R., Eisenhauer, P., Mack, D., Brown, C., Filice, G. and Spitalny, G. (1989 a). Immune responses associated with early survival after peroral infection with Toxoplasma gondii. Journal of Immunology 142, 3247–3255.CrossRefGoogle ScholarPubMed
McLeod, R., Estes, R. G., Mack, D. G. and Cohen, H. (1984). Immune response of mice to ingested Toxoplasma gondii. A model of Toxoplasma infection acquired by ingestion. Journal of Infectious Diseases 149, 234–244.CrossRefGoogle Scholar
McLeod, R., Skamene, E., Brown, C. R., Eisenhauer, P. and Mack, D. G. (1989 b). Genetic regulation on early survival and cyst number after peroral Toxoplasma gondii infection of AxB/ BxA recombinant inbred and B10 congenic mice. Journal of Immunology 143, 3031–3034.CrossRefGoogle ScholarPubMed
Muñoz, M., Heimesaat, M. M., Danker, K., Struck, D., Lohmann, U., Plickert, R., Bereswill, S., Fischer, A., Dunay, I. R., Wolk, K., Loddenkemper, C., Krell, H. W., Libert, C., Lund, L. R., Frey, O., Hölscher, C., Iwakura, Y., Ghilardi, N., Ouyang, W., Kamradt, T., Sabat, R. and Liesenfeld, O. (2009). Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. Journal of Experimental Medicine 206, 3047–3059.CrossRefGoogle ScholarPubMed
Parmley, S. F., Gross, U., Sucharczuk, A., Windeck, T., Sgarlato, G. D. and Remington, J. S. (1994). Two alleles of the gene encoding surface antigen P22 in 25 strains of Toxoplasma gondii. Journal of Parasitology 80, 293–301.CrossRefGoogle ScholarPubMed
Pomares, C., Ajzenberg, D., Bornard, L., Bernardin, G., Hasseine, L., Dardé, M. L. and Marty, P. (2011). Toxoplasmosis and horse meat, France. Emerging Infectious Diseases 17, 1327–1328.CrossRefGoogle ScholarPubMed
Rachinel, N., Buzoni-Gatel, D., Dutta, C., Mennechet, F. J., Luangsay, S., Minns, L. A., Grigg, M. E., Tomavo, S., Boothroyd, J. C. and Kasper, L. H. (2004). The induction of acute ileitis by a single microbial antigen of Toxoplasma gondii. Journal of Immunology 173, 2725–2735.CrossRefGoogle ScholarPubMed
Remington, J. S., McLeod, R., Thulliez, P. and Desmonts, G. (2006). Toxoplasmosis. In Infectious Diseases of the Fetus and Newborn Infant (ed. Remington, J. S., Klein, J. S., Wilson, C. B. and Baker, C. J.), pp. 947–1091. Elsevier Saunders, Philadelphia, PA, USA.CrossRefGoogle Scholar
Schreiner, M. and Liesenfeld, O. (2009). Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature. Memorias do Instituto Oswaldo Cruz 104, 221–233.CrossRefGoogle Scholar
Speer, C. A. and Dubey, J. P. (1998). Ultrastructure of early stages of infection in mice fed Toxoplasma gondii oocysts. Parasitology 116, 35–42.CrossRefGoogle ScholarPubMed
Tan, T. G., Mui, E., Cong, H., Witola, W. H., Montpetit, A., Muench, S. P., Sidney, J., Alexander, J., Sette, A., Grigg, M. E., Maewal, A. and McLeod, R. (2010). Identification of T. gondii epitopes, adjuvants, and host genetic factors that influence protection of mice and humans. Vaccine 28, 3977–3989.CrossRefGoogle ScholarPubMed
Velmurugan, G. V., Su, C. and Dubey, J. P. (2009). Isolate designation and characterization of Toxoplasma gondii isolates from pigs in the United States. Journal of Parasitology 95, 95–99.CrossRefGoogle ScholarPubMed
Witola, W. H., Mui, E., Hargrave, A., Liu, S., Hypolite, M., Montpetit, A., Cavailles, P., Bisanz, C., Cesbron-Delauw, M. F., Fournie, G. J. and McLeod, R. (2011). NALP1 influences susceptibility to human congenital toxoplasmosis, Proinflammatory cytokine response, and fate of Toxoplasma gondii-infected monocytic cells. Infection and Immunity 79, 756–766.CrossRefGoogle ScholarPubMed