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Cellular and molecular physiopathology of congenital toxoplasmosis: The dual role of IFN-γ

Published online by Cambridge University Press:  25 October 2007

A. W. PFAFF ,
A. ABOU-BACAR ,
V. LETSCHER-BRU ,
O. VILLARD ,
A. SENEGAS ,
M. MOUSLI  and
E. CANDOLFI
A. W. PFAFF
Affiliation:
Institut de Parasitologie et de Pathologie Tropicale, EA 3950, Université Louis Pasteur, 3 rue Koeberlé, 67000, Strasbourg, France
A. ABOU-BACAR
Affiliation:
Institut de Parasitologie et de Pathologie Tropicale, EA 3950, Université Louis Pasteur, 3 rue Koeberlé, 67000, Strasbourg, France
V. LETSCHER-BRU
Affiliation:
Institut de Parasitologie et de Pathologie Tropicale, EA 3950, Université Louis Pasteur, 3 rue Koeberlé, 67000, Strasbourg, France
O. VILLARD
Affiliation:
Institut de Parasitologie et de Pathologie Tropicale, EA 3950, Université Louis Pasteur, 3 rue Koeberlé, 67000, Strasbourg, France
A. SENEGAS
Affiliation:
Institut de Parasitologie et de Pathologie Tropicale, EA 3950, Université Louis Pasteur, 3 rue Koeberlé, 67000, Strasbourg, France
M. MOUSLI
Affiliation:
Institut de Parasitologie et de Pathologie Tropicale, EA 3950, Université Louis Pasteur, 3 rue Koeberlé, 67000, Strasbourg, France
E. CANDOLFI*
Affiliation:
Institut de Parasitologie et de Pathologie Tropicale, EA 3950, Université Louis Pasteur, 3 rue Koeberlé, 67000, Strasbourg, France
*
*Corresponding author: Ermanno Candolfi, Institut de Parasitologie et de Pathologie Tropicale, EA 3950, Université Louis Pasteur de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France. Tel: +33-(0)390243679. Fax: +33-(0)390243693. E-mail: [email protected]
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Summary

Toxoplasma gondii is one of the few pathogens that can cross the placenta. Frequency and severity of transmission vary with gestational age. While the control of acquired toxoplasmosis is already well explored, the control of materno-foetal transmission of the parasite remains almost unknown. This is partly due to the lack of an animal model to study this process. This review summarises the studies which have been undertaken and shows that the mouse is a valuable model despite obvious differences to the human case. The paramount role of the cellular immune response has been shown by several experiments. However, IFN-γ has a dual role in this process. While its beneficial effects in the control of toxoplasmosis are well known, it also seems to have transmission-enhancing effects and can also directly harm the developing foetus. The ultimate goal of these studies is to develop a vaccine which protects both mother and foetus. Therefore, it is useful to study the mechanisms of natural resistance against transmission during a secondary infection. In this setting, the process is more complicated, involving both cellular and also humoral components of the immune system. In summary, even if the whole process is far from being elucidated, important insights have been gained so far which will help us to undertake rational vaccine research.

Keywords

Toxoplasma gondiicongenital infectionInterferon-γinflammationvaccine
Type
Research Article
Information
Parasitology , Volume 134 , Special Issue 13: PARASITES IN PREGNANCY , December 2007 , pp. 1895 - 1902
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

Abbasi, M., Kowalewska-Grochowska, K., Bahar, M. A., Kilani, R. T., Winkler-Lowen, B. and Guilbert, L. J. (2003). Infection of placental trophoblasts by Toxoplasma gondii. Journal of Infectious Diseases 188, 608–616.CrossRefGoogle ScholarPubMed
Abou-Bacar, A., Pfaff, A. W., Georges, S., Letscher-Bru, V., Filisetti, D., Villard, O., Antoni, E., Klein, J. P. and Candolfi, E. (2004 a). Role of NK cells and gamma interferon in transplacental passage of Toxoplasma gondii in a mouse model of primary infection. Infection and Immunity 72, 1397–1401.CrossRefGoogle Scholar
Abou-Bacar, A., Pfaff, A. W., Letscher-Bru, V., Filisetti, D., Rajapakse, R., Antoni, E., Villard, O., Klein, J. P. and Candolfi, E. (2004 b). Role of gamma interferon and T cells in congenital Toxoplasma transmission. Parasite Immunology 26, 315–318.CrossRefGoogle Scholar
Ajzenberg, D., Cogne, N., Paris, L., Bessieres, M. H., Thulliez, P., Filisetti, D., Pelloux, H., Marty, P. and Darde, M. L. (2002). Genotype of 86 Toxoplasma gondii isolates associated with human congenital toxoplasmosis, and correlation with clinical findings. Journal of Infectious Diseases 186, 684–689.CrossRefGoogle ScholarPubMed
Caetano, B. C., Bruna-Romero, O., Fux, B., Mendes, E. A., Penido, M. L. and Gazzinelli, R. T. (2006). Vaccination with replication-deficient recombinant adenoviruses encoding the main surface antigens of Toxoplasma gondii induces immune response and protection against infection in mice. Human Gene Therapy 17, 415–426.CrossRefGoogle ScholarPubMed
Couper, K. N., Nielsen, H. V., Petersen, E., Roberts, F., Roberts, C. W. and Alexander, J. (2003). DNA vaccination with the immunodominant tachyzoite surface antigen (SAG-1) protects against adult acquired Toxoplasma gondii infection but does not prevent maternofoetal transmission. Vaccine 21, 2813–2820.CrossRefGoogle Scholar
Denkers, E. Y. (1999). T lymphocyte-dependent effector mechanisms of immunity to Toxoplasma gondii. Microbes and Infection 1, 699–708.CrossRefGoogle ScholarPubMed
Denkers, E. Y. and Gazzinelli, R. T. (1998). Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clinical Microbiology Reviews 11, 569–588.CrossRefGoogle ScholarPubMed
Derouin, F., Bultzel, C. and Roze, S. (2005). Toxoplasmose: état des connaissances et évaluation du risque lié à l'alimentation. Paris, Agence Française de Sécurité Sanitaire des Aliments.Google Scholar
Desmonts, G. and Couvreur, J. (1979). Congenital toxoplasmosis. A prospective study of the offspring of 542 women who acquired toxoplasmosis during pregnancy. Perinatal Medicine, Sixth European Congress (ed. Thalhammer, O., Baumgarten, K. and Pollak, A.), pp. 51–60. Georg Thieme, Stuttgart, Germany.Google Scholar
Dimier-Poisson, I., Aline, F., Bout, D. and Mevelec, M. N. (2006). Induction of protective immunity against toxoplasmosis in mice by immunization with Toxoplasma gondii RNA. Vaccine 24, 1705–1709.CrossRefGoogle ScholarPubMed
Dubey, J. P. (1987). Toxoplasma gondii cysts in placentas of experimentally infected sheep. American Journal of Veterinary Research 48, 352–353.Google ScholarPubMed
Dunn, D., Wallon, M., Peyron, F., Petersen, E., Peckham, C. and Gilbert, R. (1999). Mother-to-child transmission of toxoplasmosis: risk estimates for clinical counselling. Lancet 353, 1829–1833.CrossRefGoogle ScholarPubMed
Entrican, G. (2002). Immune regulation during pregnancy and host-pathogen interactions in infectious abortion. Journal of Comparative Pathology 126, 79–94.CrossRefGoogle ScholarPubMed
Ferro, E. A., Silva, D. A., Bevilacqua, E. and Mineo, J. R. (2002). Effect of Toxoplasma gondii infection kinetics on trophoblast cell population in Calomys callosus, a model of congenital toxoplasmosis. Infection and Immunity 70, 7089–7094.CrossRefGoogle Scholar
Fricker-Hidalgo, H., Pelloux, H., Racinet, C., Grefenstette, I., Bost-Bru, C., Goullier-Fleuret, A. and Ambroise-Thomas, P. (1998). Detection of Toxoplasma gondii in 94 placentae from infected women by polymerase chain reaction, in vivo, and in vitro cultures. Placenta 19, 545–549.CrossRefGoogle ScholarPubMed
Georgiades, P., Ferguson-Smith, A. C. and Burton, G. J. (2002). Comparative developmental anatomy of the murine and human definitive placentae. Placenta 23, 3–19.CrossRefGoogle ScholarPubMed
Hauser, W. E. Jr. and Tsai, V. (1986). Acute Toxoplasma infection of mice induces spleen NK cells that are cytotoxic for Toxoplasma gondii in vitro. Journal of Immunology 136, 313–319.CrossRefGoogle ScholarPubMed
Hunt, J. S., Petroff, M. G., McIntire, R. H. and Ober, C. (2005). HLA-G and immune tolerance in pregnancy. FASEB Journal 19, 681–693.CrossRefGoogle ScholarPubMed
Ismael, A. B., Dimier-Poisson, I., Lebrun, M., Dubremetz, J. F., Bout, D. and Mevelec, M. N. (2006). Mic1-3 knockout of Toxoplasma gondii is a successful vaccine against chronic and congenital toxoplasmosis in mice. Journal of Infectious Diseases 194, 1176–1183.CrossRefGoogle ScholarPubMed
Letscher-Bru, V., Pfaff, A. W., Abou-Bacar, A., Filisetti, D., Antoni, E., Villard, O., Klein, J. P. and Candolfi, E. (2003). Vaccination with Toxoplasma gondii SAG-1 protein is protective against congenital toxoplasmosis in BALB/c mice but not in CBA/J mice. Infection and Immunity 71, 6615–6619.CrossRefGoogle ScholarPubMed
Mevelec, M. N., Bout, D., Desolme, B., Marchand, H., Magne, R., Bruneel, O. and Buzoni-Gatel, D. (2005). Evaluation of protective effect of DNA vaccination with genes encoding antigens GRA4 and SAG1 associated with GM-CSF plasmid, against acute, chronical and congenital toxoplasmosis in mice. Vaccine 23, 4489–4499.CrossRefGoogle ScholarPubMed
Minkoff, H., Remington, J. S., Holman, S., Ramirez, R., Goodwin, S. and Landesman, S. (1997). Vertical transmission of toxoplasma by human immunodeficiency virus-infected women. American Journal of Obstetrics and Gynecology 176, 555–559.CrossRefGoogle ScholarPubMed
Moffett, A. and Loke, Y. W. (2004). The immunological paradox of pregnancy: a reappraisal. Placenta 25, 1–8.CrossRefGoogle ScholarPubMed
Munn, D. H., Zhou, M., Attwood, J. T., Bondarev, I., Conway, S. J., Marshall, B., Brown, C. and Mellor, A. L. (1998). Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281, 1191–1193.CrossRefGoogle ScholarPubMed
Ng, S. C., Gilman-Sachs, A., Thaker, P., Beaman, K. D., Beer, A. E. and Kwak-Kim, J. (2002). Expression of intracellular Th1 and Th2 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy. American Journal of Reproductive Immunology 48, 77–86.CrossRefGoogle ScholarPubMed
Pfaff, A. W., Georges, S., Abou-Bacar, A., Letscher-Bru, V., Klein, J. P., Mousli, M. and Candolfi, E. (2005 a). Toxoplasma gondii regulates ICAM-1 mediated monocyte adhesion to trophoblasts. Immunology and Cell Biology 83, 483–489.CrossRefGoogle ScholarPubMed
Pfaff, A. W., Villard, O., Klein, J. P., Mousli, M. and Candolfi, E. (2005 b). Regulation of Toxoplasma gondii multiplication in BeWo trophoblast cells: cross-regulation of nitric oxide production and polyamine biosynthesis. International Journal for Parasitology 35, 1569–1576.CrossRefGoogle ScholarPubMed
Remington, J. S., McLeod, R., Thulliez, P. and Desmonts, G. (2000). Toxoplasmosis. In Diseases of the Fetus and Newborn Infant (ed. Remington, J. S. and Klein, J. O.), pp. 205–346. Philadelphia: W. B. Saunders Company.Google Scholar
Roberts, C. W. and Alexander, J. (1992). Studies on a murine model of congenital toxoplasmosis: vertical disease transmission only occurs in BALB/c mice infected for the first time during pregnancy. Parasitology 104, 19–23.CrossRefGoogle ScholarPubMed
Roberts, C. W., Brewer, J. M. and Alexander, J. (1994). Congenital toxoplasmosis in the Balb/c mouse: prevention of vertical disease transmission and fetal death by vaccination. Vaccine 12, 1389–1394.CrossRefGoogle ScholarPubMed
Ruiz, S., Beauvillain, C., Mevelec, M. N., Roingeard, P., Breton, P., Bout, D. and Dimier-Poisson, I. (2005). A novel CD4-CD8alpha+CD205+CD11b- murine spleen dendritic cell line: establishment, characterization and functional analysis in a model of vaccination to toxoplasmosis. Cellular Microbiology 7, 1659–1671.CrossRefGoogle Scholar
Sher, A., Collazzo, C., Scanga, C., Jankovic, D., Yap, G. and Aliberti, J. (2003). Induction and regulation of IL-12-dependent host resistance to Toxoplasma gondii. Immunology Research 27, 521–528.CrossRefGoogle ScholarPubMed
Staun-Ram, E. and Shalev, E. (2005). Human trophoblast function during the implantation process. Reproductive Biology and Endocrinology 3, 56.CrossRefGoogle ScholarPubMed
Szekeres-Bartho, J. (2002). Immunological relationship between the mother and the fetus. International Reviews in Immunology 21, 471–495.CrossRefGoogle ScholarPubMed