Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-14T15:19:38.928Z Has data issue: false hasContentIssue false
  • English
  • Français

Cellular and immunological basis of the host-parasite relationship during infection with Neospora caninum

Published online by Cambridge University Press:  06 June 2006

A. HEMPHILL ,
N. VONLAUFEN  and
A. NAGULESWARAN
A. HEMPHILL
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
N. VONLAUFEN
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
A. NAGULESWARAN
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
Get access Rights & Permissions [Opens in a new window]

Abstract

Neospora caninum is an apicomplexan parasite that is closely related to Toxoplasma gondii, the causative agent of toxoplasmosis in humans and domestic animals. However, in contrast to T. gondii, N. caninum represents a major cause of abortion in cattle, pointing towards distinct differences in the biology of these two species. There are 3 distinct key features that represent potential targets for prevention of infection or intervention against disease caused by N. caninum. Firstly, tachyzoites are capable of infecting a large variety of host cells in vitro and in vivo. Secondly, the parasite exploits its ability to respond to alterations in living conditions by converting into another stage (tachyzoite-to-bradyzoite or vice versa). Thirdly, by analogy with T. gondii, this parasite has evolved mechanisms that modulate its host cells according to its own requirements, and these must, especially in the case of the bradyzoite stage, involve mechanisms that ensure long-term survival of not only the parasite but also of the host cell. In order to elucidate the molecular and cellular bases of these important features of N. caninum, cell culture-based approaches and laboratory animal models are being exploited. In this review, we will summarize the current achievements related to host cell and parasite cell biology, and will discuss potential applications for prevention of infection and/or disease by reviewing corresponding work performed in murine laboratory infection models and in cattle.

Keywords

Neospora caninumhost cell invasioncell surface receptorshost cell modulationstage conversionmurine modelvaccination
Type
Review Article
Information
Parasitology , Volume 133 , Issue 3 , September 2006 , pp. 261 - 278
Copyright
2006 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

REFERENCES

Alaeddine, F., Keller, N., Leepin, A. and Hemphill, A. ( 2005). Reduced infection and protection from clinical signs of cerebral neosporosis in C57BL/6 mice vaccinated with the recombinant microneme antigen NcMIC1. Journal of Parasitology 91, 657–665.CrossRefGoogle Scholar
Alexander, J., Scharton-Kersten, T. M., Yap, G., Roberts, C. W., Liew, F. Y. and Sher, A. ( 1997). Mechanisms of innate resistance to Toxoplasma gondii. Philososphical Transactions of the Royal Societey London 352, 1355–1359.CrossRefGoogle Scholar
Andrianarivo, A. G., Choromonaski, L., McDonough, S. P., Packham, A. E. and Conrad, P. A. ( 1999). Immunogenicity of a killed whole Neospora caninum tachyzoite preparation formulated with different adjuvants. International Journal for Parasitology 29, 1613–1625.CrossRefGoogle Scholar
Athanassakis, I. and Iconomidou, B. ( 1996). Cytokine production in the serum and spleen of mice from day 6 to 14 of gestation: cytokines/placenta/spleen/serum. Developmental Immunology 4, 247–255.Google Scholar
Atkinson, R., Harper, P. A., Ryce, C., Morrison, D. A. and Ellis, J. T. ( 1999). Comparison of the biological characteristics of two isolates of Neospora caninum. Parasitology 118, 363–370.CrossRefGoogle Scholar
Barber, J. S., Homdahl, O. J., Owen, M. R., Guy, F., Uggla, A. and Trees, A. J. ( 1995). Characterization of the first European isolate of Neospora caninum (Dubey, Carpenter, Speer, Topper and Uggla). Parasitology 111, 563–568.CrossRefGoogle Scholar
Baszler, T. V., Adams, S., Vander-Schalie, J., Mathison, B. A. and Kostovic, M. ( 2001). Validation of a commercially available monoclonal antibody-based competitive-inhibition enzyme-linked immunosorbent assay for detection of serum antibodies to Neospora caninum in cattle. Journal of Clinical Microbiology 39, 3851–3857.CrossRefGoogle Scholar
Baszler, T. V., Knowles, D. P., Dubey, J. P., Gay, J. M., Mathison, B. A. and McElwain, T. F. ( 1996). Serological diagnosis of bovine neosporosis by Neospora caninum monoclonal antibody-based competitive inhibition enzyme-linked immunosorbent assay. Journal of Clinical Microbiology 34, 1423–1428.Google Scholar
Baszler, T. V., Long, M. T., Mcelwain, T. F. and Mathison, B. A. ( 1999). Interferon-gamma and interleukin-12 mediate protection to acute Neospora caninum infection in BALB/c mice. International Journal for Parasitology 29, 1635–1646.CrossRefGoogle Scholar
Beckers, C. J., Dubremetz, J. F., Mercereau-Puijalon, O. and Joiner, K. A. ( 1999). The Toxoplasma gondii rhoptry protein ROP 2 is inserted into the parasitophorous vacuole membrane, surrounding the intracellular parasite, and is exposed to the host cell cytoplasm. Journal of Cell Biology 27, 947–961.Google Scholar
Binder, E. M. and Kim, K. ( 2004). Location, location, location: trafficking and function of secreted proteases of Toxoplasma and Plasmodium. Traffic 5, 914–924.CrossRefGoogle Scholar
Bjerkås, I., Mohn, S. F. and Presthus, J. ( 1984). Unidentified cyst-forming sporozoon causing encephalomyelitis and myositis in dogs. Zeitschrift für Parasitenkunde 70, 271–274.CrossRefGoogle Scholar
Björkman, C., Johansson, O., Stenlund, S., Holmdahl, O. J. M. and Uggla, A. ( 1996). Neospora species infection in a herd of dairy cattle. Journal of the American Veterinary Medical Association 208, 1441–1444.Google Scholar
Bohne, W., Heesemann, J. and Gross, U. ( 1994). Reduced replication of Toxoplasma gondii is necessary for induction of bradyzoite-specific antigens: a possible role for nitric oxide in triggering stage conversion. Infection and Immunity 62, 1761–1767.Google Scholar
Boysen, P., Klevar, S., Olsen, I., and Storset, A. K. ( 2006). The protozoan Neospora caninum directly triggers bovine NK cells to produce gamma interferon and to kill infected fibroblasts. Infection and Immunity 74, 953–960.CrossRefGoogle Scholar
Butcher, B. A. and Denkers, E. Y. ( 2002). Mechanism of entry determines the ability of Toxoplasma gondii to inhibit macrophage proinflammatory cytokine production. Infection and Immunity 70, 5216–5224.CrossRefGoogle Scholar
Buxton, D., McAllister, M. M. and Dubey, J. P. ( 2002). The comparative pathogenesis of neosporosis. Trends Parasitology 18, 546–552.CrossRefGoogle Scholar
Cannas, A., Naguleswaran, A., Müller, N., Gottstein, B., Eperon, S. and Hemphill, A. ( 2003 a). Vaccination of mice against experimental N. caninum infection using NcSAG1- and NcSRS2-based recombinant antigens and DNA-vaccines. Parasitology 126, 303–312.Google Scholar
Cannas, A., Naguleswaran, A., Müller, N., Gottstein, B. and Hemphill, A. ( 2003 b). Protective effect of vaccination with recombinant microneme protein NcMIC3 in mice following challenge infection with Neospora caninum tachyzoites. Journal of Parasitology 89, 44–50.Google Scholar
Carruthers, V. B. ( 2002). Host cell invasion by the opportunistic pathogen Toxoplasma gondii. Acta Tropica 81, 111–122.CrossRefGoogle Scholar
Carruthers, V. B. and Blackman, M. J. ( 2005). A new release on life: emerging concepts in proteolysis and parasite invasion. Molecular Microbiology 55, 1617–1630.CrossRefGoogle Scholar
Cesbron-Delauw, M. F., Lecordier, L. and Mercier, C. ( 1996). Role of secretory dense granule organelles in the pathogenesis of toxoplasmosis. Current Topics in Microbiology and Immunology 219, 59–65.CrossRefGoogle Scholar
Choromanski, L. J. ( 2002). Neospora caninum vaccine field safety evaluation. Intervet Bulletin 1–3.Google Scholar
Cole, R. A., Lindsay, D. S., Blagburn, B. L. and Dubey, J. P. ( 1995). Vertical transmission of Neospora caninum in mice. Journal of Parasitology 81, 730–732.CrossRefGoogle Scholar
Cooper, C. E. ( 1999). Nitric oxide and iron proteins. Biochimica et Biophysica Acta 1411, 290–309.CrossRefGoogle Scholar
Darcy, F. and Santoro, F. ( 1994). Toxoplasmosis. In Parasitic Infections and the Immune System ( ed. Kierszenbaum, F.), pp. 163–190. Academic Press, New York.CrossRef
Davison, H. C., Otter, A. and Trees, A. J. ( 1999). Estimation of vertical and horizontal transmission parameters of Neospora caninum infections in dairy cattle. International Journal for Parasitology 29, 1683–1689.CrossRefGoogle Scholar
Denkers, E. Y., Butcher, B. A., Del Rio, L. and Kim, L. ( 2004). Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signaling cascades during intracellular Toxoplasma gondii infection. Immunology Review 201, 191–205.CrossRefGoogle Scholar
Dijkstra, T., Barkema, H. W., Eysker, M. and Wouda, W. ( 2001). Evidence of post-natal transmission of Neospora caninum in Dutch dairy herds. International Journal for Parasitology 31, 209–215.CrossRefGoogle Scholar
Dowse, T. J., Pascall, J. C., Brown, K. D. and Soldati, D. ( 2005). Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion. International Journal for Parasitology 35, 747–756.CrossRefGoogle Scholar
Dowse, T. J. and Soldati, D. ( 2004). Host cell invasion by the apicomplexans: the significance of microneme protein proteolysis. Current Opinion in Microbiology 7, 388–396.CrossRefGoogle Scholar
Dubey, J. P. ( 2003). Review of Neospora caninum and neosporosis in animals. The Korean Journal of Parasitology 41, 1–16.CrossRefGoogle Scholar
Dubey, J. P., Barr, B. C., Barta, J. R., Bjerkas, I., Bjorkman, C., Blagburn, B. L., Bowman, D. D., Buxton, D., Ellis, J. T., Gottstein, B., Hemphill, A., Hill, D. E., Howe, D. K., Jenkins, M. C., Kobayashi, Y., Koudela, B., Marsh, A. E., Mattsson, J. G., McAllister, M. M., Modry, D., Omata, Y., Sibley, L. D., Speer, C. A., Trees, A. J., Uggla, A., Upton, S. J., Williams, D. J. and Lindsay, D. S. ( 2002). Redescription of Neospora caninum and its differentiation from related coccidia. International Journal for Parasitology 32, 929–946.CrossRefGoogle Scholar
Dubey, J. P., Carpenter, J. L., Speer, C. A., Topper, M. J. and Uggla, A. ( 1988 a). Newly recognized fatal protozoan disease of dogs. Journal of the American Veterinary Medical Association 192, 1269–1285.Google Scholar
Dubey, J. P., Hattel, A. L., Lindsay, D. S. and Topper, M. J. ( 1988 b). Neonatal Neospora caninum infection in dogs: isolation of the causative agent and experimental transmission. Journal of the American Veterinary Medical Association 193, 1259–1263.Google Scholar
Dubey, J. P. and Lindsay, D. S. ( 1996). A review of Neospora caninum and neosporosis. Veterinary Parasitology 67, 1–59.CrossRefGoogle Scholar
Eperon, S., Broennimann, K., Hemphill, A. and Gottstein, B. ( 1999). Susceptibility of B-cell deficient C57BL/6 (μMT) mice to Neospora caninum infection. Parasite Immunology 21, 225–236.CrossRefGoogle Scholar
Fernandez-Garcia, A., Risco-Castillo, V., Zaballos, A., Alvarez-Garcia, G. and Ortega-Mora, L. M. ( 2005). Identification and molecular cloning of the Neospora caninum SAG4 gene specifically expressed at bradyzoite stage. Molecular and Biochemical Parasitology [Epub ahead of print].
French, N. P., Clancy, D., Davison, H. C. and Trees, A. J. ( 1999). Mathematical models of Neospora caninum infection in dairy cattle: transmission and options for control. International Journal for Parasitology 29, 1691–1704.CrossRefGoogle Scholar
Fuchs, N., Bütikofer, P., Sonda, S. and Hemphill, A. ( 1999). Detection of surface-associated and intracellular glycoconjugates and glycoproteins in Neospora caninum tachyzoites. International Journal for Parasitology 29, 1597–1611.CrossRefGoogle Scholar
Gazzinelli, R. T., Amichay, D., Sharton-Kersten, T., Grunwald, E., Farber, J. M. and Sher, A. ( 1996). Role of macrophage-derived cytokines in the induction and regulation of cell-mediated immunity to Toxoplasma gondii. Current Topics in Microbiology and Immunology 219, 127–139.CrossRefGoogle Scholar
Goebel, S., Gross, U. and Luder, C. G. ( 2001). Inhibition of host cell apoptosis by Toxoplasma gondii is accompanied by reduced activation of the caspase cascade and alterations of poly(ADP-ribose) polymerase expression. Journal of Cell Science 114, 3495–3505.Google Scholar
Gondim, M., McAllister, M. M., Anderson-Sprecher, R. C., Björkman, C., Locks, T. F., Firkins, L. D., Gao, L. and Fisxher, W. R. ( 2005). Transplacental transmission and abortion in cows administred Neospora caninum oocysts. Journal of Parasitology 90, 1394–1400.Google Scholar
Gondim, M., McAllister, M. M., Pitt, W. C. and Zemlicka, D. E. ( 2004). Coyotes (Canis latrans) are definitive hosts of Neospora caninum. International Journal for Parasitology 34, 159–161.CrossRefGoogle Scholar
Graham, D. A., Calvert, V., Whyte, M. and Marks, J. ( 1999). Absence of serological evidence for human Neospora caninum infection. Veterinary Record 144, 672–673.CrossRefGoogle Scholar
Guy, C. S., Williams, D. J. L., Kelley, D. F., McGarry, J. W., Guy, F., Bjorkman, C., Smith, R. F. and Trees, A. J. ( 2001). Neospora caninum in persitently infected, pregnant cows: spontaneous transplacental infection is associated with an acute increase in maternal antibody. Veterinary Record 149, 443–449.CrossRefGoogle Scholar
Haldorson, G. J., Mathison, B. A., Wenberg, K., Conrad, P. A., Dubey, J. P., Trees, A. J., Yamane, I. and Baszler, T. V. ( 2005). Immunization with native surface protein NcSRS2 induces a Th2 immune response and reduces congenital Neospora caninum transmission in mice. International Journal for Parasitology 35, 1407–1415.CrossRefGoogle Scholar
Hemphill, A. ( 1996). Subcellular localization and functional characterization of Nc-p43, a major Neospora caninum tachyzoite surface protein. Infection and Immunity 64, 4279–4287.Google Scholar
Hemphill, A. ( 1999). The host-parasite relationship in neosporosis. Advances in Parasitology 43, 47–104.CrossRefGoogle Scholar
Hemphill, A., Gajendran, N., Sonda, S., Fuchs, N., Gottstein, B., Hentrich, B. and Jenkins, M. ( 1998). Identification and characterization of a dense granule-associated protein in Neospora caninum tachyzoites. International Journal for Parasitology 28, 429–438.CrossRefGoogle Scholar
Hemphill, A. and Gottstein, B. ( 2000). A European perspective on Neospora caninum. International Journal for Parasitology 30, 877–924.CrossRefGoogle Scholar
Hemphill, A., Gottstein, B. and Kaufmann, H. ( 1996). Adhesion and invasion of bovine endothelial cells by Neospora caninum. Parasitology 112, 183–197.CrossRefGoogle Scholar
Hemphill, A., Fuchs, N., Sonda, S., Gottstein, B. and Hentrich, B. ( 1997). Identification and partial characterization of a 36 kD surface protein on Neospora caninum tachyzoites. Parasitology 115, 371–380.CrossRefGoogle Scholar
Hemphill, A., Vonlaufen, N., Naguleswaran, A., Keller, N., Riesen, M., Guetg, N., Srinivasan, S. and Alaeddine, F. ( 2004). Tissue culture and explant approaches to studying and visualizing Neospora caninum and its interactions with the host cell. Microscopy and Microanalysis 10, 602–620.CrossRefGoogle Scholar
Heussler, V., Küenzi, P. and Rottenberg, S. ( 2001). Inhibition of apoptosis by intracellular protozoan parasites. International Journal for Parasitology 31, 1166–1176.CrossRefGoogle Scholar
Heydorn, A. O. and Mehlhorn, H. ( 2002). A re-evaluation of Neospora and Hammondia spp. Trends in Parasitology 18, 246.CrossRefGoogle Scholar
Hisaeda, H., Sakai, T., Ishikawa, H., Maekawa, ,Y., Yasumoto, K., Good, R. A. and Himeno, K. ( 1997). Heat shock protein 65 induced by gamma delta T cells prevents apoptosis of macrophages and contributes to host defense in mice infected with Toxoplasma gondii. Journal of Immunology 159, 2375–2378.Google Scholar
Hisaeda, H., Sakai, T., Nagasawa, H., Ishikawa, H., Yasutomo, K., Maekawa, Y. and Himeno, K. ( 1996). Contribution of extrathymic interferon gamma delta T cells to the expression of heat shock protein and to protective immunity in mice infected with Toxoplasma gondii. Immunology 88, 551–557.Google Scholar
Howe, D. K. and Sibley, L. D. ( 1995). Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. Journal of Infectious Diseases 172, 1561–1566.CrossRefGoogle Scholar
Howe, D. K., Crawford, A. C., Lindsay, D. and Sibley, L. D. ( 1998). The p29 and p35 immunodominant antigens of Neospora caninum tachyzoites are homologous to the family of surface antigens of Toxoplasma gondii. Infection and Immunity 66, 5322–5328.Google Scholar
Innes, E. A., Andrianarivo, A. G., Björkman, C., Williams, D. J. and Conrad, P. A. ( 2002). Immune responses to Neospora caninum and prospects for vaccination. Trends in Parasitology 18, 497–504.CrossRefGoogle Scholar
Innes, E. A., Buxton, D., Eperon, S. and Gottstein, B. ( 2000). Immunology of Neospora caninum infection in cattle and mice. International Journal for Parasitology 30, 896–900.Google Scholar
Innes, E. A., Wright, S. E., Maley, S., Rae, A., Schock, A., Kirvar, E., Bartley, P., Hamilton, C., Carey, I. M. and Buxton, D. ( 2001). Protection against vertical transmission in bovine neosporosis. International Journal for Parasitology 31, 1523–1534.CrossRefGoogle Scholar
Innes, E. A., Wright, S., Bartley, P., Maley, S., Macaldowie, C., Esteban Redondo, I. and Buxton, D. ( 2005). The host-parasite relationship in bovine neosporosis. Veterinary Immunology and Immunopathology 108, 29–36.CrossRefGoogle Scholar
Jenkins, M., Parker, C., Tuo, W., Vinyard, B. and Dubey, J. P. ( 2004). Inclusion of Cpg adjuvant with plasmid DNA coding for NcGRA7 improves protection against congenital neosprosis. Infection and Immunity 72, 1817–1819.CrossRefGoogle Scholar
Kano, R., Masukata, Y., Omata, Y., Kobayashi, Y., Maeda, R. and Saito, A. ( 2005). Relationship between type 1/type 2 immune responses and occurrence of vertical transmission in Balb/c mice infected with Neospora caninum. Veterinary Parasitology 129, 159–164.CrossRefGoogle Scholar
Kasper, L. H. and Kahn, I. A. ( 1998). Antigen-specific CD8+ T-cells protect against lethal toxoplasmosis in mice infected with Neospora caninum. Infection and Immunity 66, 1554–1560.Google Scholar
Keeley, A. and Soldati, D. ( 2004). The glideosome: a molecular machine powering motility and host-cell invasion by Apicomplexa. Trends in Cell Biology 14, 528–532.CrossRefGoogle Scholar
Keller, N., Naguleswaran, A., Cannas, A., Vonlaufen, N., Bienz, M., Björkman, C., Bohne, W. and Hemphill, A. ( 2002). Identification of a Neospora caninum microneme protein (NcMIC1) which interacts with sulfated host cell surface glycosaminoglycans. Infection and Immunity 70, 3187–3198.CrossRefGoogle Scholar
Keller, N., Riesen, M., Naguleswaran, A., Vonlaufen, N., Stettler, R., Leepin, A., Wastling, J. M. and Hemphill, A. ( 2004). Identification and characterization of a Neospora caninum microneme-associated protein (NcMIC4) that exhibits unique lactose-binding properties. Infection and Immunity 72, 4791–4800.CrossRefGoogle Scholar
Khan, I. A., Schwartzman, J. D., Fonseka, S. and Kasper, L. H. ( 1997). Neospora caninum: role for immune cytokines in host immunity. Experimental Parasitology 85, 24–34.CrossRefGoogle Scholar
Kim, K. ( 2004). Role of proteases in host cell invasion by Toxoplasma gondii and other apicomplexa. Acta Tropica 91, 69–81.CrossRefGoogle Scholar
Kirkman, L. A., Weiss, L. M. and Kim, K. ( 2001). Cyclic nucleotide signaling in Toxoplasma gondii bradyzoite differentiation. Infection and Immunity 69, 148–153.CrossRefGoogle Scholar
Lecordier, L., Mercier, C., Sibley, L. D. and Cesbron-Delauw, M. F. ( 1999). Transmembrane insertion of the Toxoplasma gondii GRA5 protein occurs after soluble secretion into the host cell. Molecular Biology of the Cell 10, 1277–1287.CrossRefGoogle Scholar
Lei, Y., Davey, M. and Ellis, J. T. ( 2005 a). Attachment and invasion of Toxoplasma gondii and Neospora caninum to epithelial and fibroblast cell lines in vitro. Parasitology 131, 583–590.Google Scholar
Lei, Y., Birch, D., Davey, M. and Ellis, J. T. ( 2005 b). Subcellular fractionation and molecular characterization of the pellicle and plasmalemma of Neospora caninum. Parasitology 131, 467–475.Google Scholar
Liddell, S., Jenkins, M., Collica, C. M. and Dubey, J. P. ( 1999). Prevention of vertical transfer of Neospora caninum in BALB/c mice by vaccination. Journal of Parasitology 85, 1072–1075.CrossRefGoogle Scholar
Liddell, S., Parker, C., Vinyard, B., Jenkins, M. and Dubey, J. P. ( 2003). Immunization of mice with plasmid DNA coding for NcGRA7 and NcHSP33 con fers partial protection against vertical transmission of Neospora caninum. Journal of Parasitology 89, 496–500.CrossRefGoogle Scholar
Lindsay, D. S. and Dubey, J. P. ( 1989). Neospora caninum (Protozoa: apicomplexa) infections in mice. Journal of Parasitology 75, 772–779.CrossRefGoogle Scholar
Lindsay, D. S., Dubey, J. P. and Duncan, R. B. ( 1999 a). Confirmation that the dog is a definitive host for Neospora caninum. Veterinary Parasitology 82, 327–333.Google Scholar
Lindsay, S. D., Lenz, R., Blagburn, B. L. and Brake, D. A. ( 1999 b). Characterization of temperature-sensitive strains of Neospora caninum in mice. Journal of Parasitology 85, 64–67.Google Scholar
Lindsay, S. D., Lenz, R., Cole, R. A. J., Dubey, J.P. and Blagburn, B. L. ( 1995). Mouse model for central nervous system Neospora caninum infections. Journal of Parasitology 81, 313–315.CrossRefGoogle Scholar
Long, M. T. and Baszler, T. V. ( 1996). Fetal loss in BALB/c mice infected with Neospora caninum. Journal of Parasitology 82, 608–611.CrossRefGoogle Scholar
Long, M. T., Baszler, T. V. and Mathison, B. A. ( 1998). Comparison of intracerebral parasite load, lesion development, and systemic cytokines in mouse strains infected with Neospora caninum. Journal of Parasitology 84, 316–320.CrossRefGoogle Scholar
Long, M. T. and Baszler, T. V. ( 2000). Neutralization of maternal IL-4 modulates congenital protozoal transmission: comparison of innate versus acquired immune responses. Journal of Immunology 164, 4768–4774.CrossRefGoogle Scholar
Louie, K. and Conrad, P. A. ( 1999). Characterization of a cDNA encoding a subtilisin-like serine protease (NC-p65) of Neospora caninum. Molecular and Biochemical Parasitology 107, 211–223.CrossRefGoogle Scholar
Louie, K., Nordhausen, R., Robinson, T. W., Barr, B. C. and Conrad, P. A. ( 2002). Characterization of a Neospora caninum protease, NcSUB1 (NC-P65), with rabbit anti-N54. Journal of Parasitology 88, 1113–1119.CrossRefGoogle Scholar
Lovett, J. L., Howe, D. K. and Sibley, L. D. ( 2000). Molecular characterization of a thrombospondin-related anonymous protein homologue in Neospora caninum. Molecular and Biochemical Parasitology 107, 33–43.CrossRefGoogle Scholar
Luder, C. G., Algner, M., Lang, C., Bleicher, N. and Gross, U. ( 2003 a). Reduced expression of the inducible nitric oxide synthase after infection with Toxoplasma gondii facilitates parasite replication in activated murine macrophages. International Journal for Parasitology 33, 833–844.Google Scholar
Luder, C. G., Lang, C., Giraldo-Velasquez, M., Algner, M., Gerdes, J. and Gross, U. ( 2003 b). Toxoplasma gondii inhibits MHC class II expression in neural antigen-presenting cells by down-regulating the class II transactivator CIITA. Journal of Neuroimmunology 134, 12–24.Google Scholar
Luder, C. G., Walter, W., Beuerle, B., Maeurer, M. J. and Gross, U. ( 2001). Toxoplasma gondii down-regulates MHC class II gene expression and antigen presentation by murine macrophages via interference with nuclear translocation of STAT1alpha. European Journal of Immunology 31, 1475–1484.3.0.CO;2-C>CrossRefGoogle Scholar
Lunden, A., Marks, J., Maley, S. W. and Innes, E. A. ( 1998). Cellular immune responses in cattle experimentally infected with Neospora caninum. Parasite Immunology 20, 519–526.CrossRefGoogle Scholar
Lunden, A., Wright, S., Allen, J. E. and Buxton, D. ( 2002). Immunisation of mice against neosporosis. International Journal for Parasitology 32, 867–876.CrossRefGoogle Scholar
Lyons, R. E., McLeod, R. and Roberts, C. W. ( 2002). Toxoplasma gondii tachyzoite-bradyzoite interconversion. Trends in Parasitology 18, 198–201.CrossRefGoogle Scholar
McAllister, M. M., Bjoerkman, C., Anderson-Sprecher, R. and Rogers, D. G. ( 2000). Evidence of point-source exposure to Neospora caninum and protective immunity in a herd of beef cows. Journal of the American Veterinary Medical Association 217, 881–887.CrossRefGoogle Scholar
McAllister, M. M., Dubey, J. P., Lindsay, D. S., Jolley, W. R., Wills, R. A. and McGuire, A. M. ( 1998). Dogs are definitive hosts of Neospora caninum. International Journal for Parasitology 28, 1473–1478.CrossRefGoogle Scholar
Mercier, C., Adjogble, K. D., Daubener, W. and Delauw, M. F. ( 2005). Dense granules: are they key organelles to help understand the parasitophorous vacuole of all apicomplexan parasites? International Journal for Parasitology 35, 8298–8249.Google Scholar
Miller, C. M., Quinn, H. E., Reichel, M. P. and Ellis, J. T. ( 2005). Reduction in transplacental transmission of Neospora caninum in outbred mice by vaccination. International Journal for Parasitology 35, 821–828.CrossRefGoogle Scholar
Molestina, R. E., Payne, T. M., Coppens, I. and Sinai, A. P. ( 2003). Activation of NF-kappaB by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated IkappaB to the parasitophorous vacuole membrane. Journal of Cell Science 116, 4359–4371.CrossRefGoogle Scholar
Molestina, R. E. and Sinai, A. P. ( 2005). Detection of a novel parasite kinase activity at the Toxoplasma gondii parasitophorous vacuole membrane capable of phophorylating host IkBa. Cellular Microbiology 7, 351–362.CrossRefGoogle Scholar
Mordue, D. G., Desai, N., Dustin, M. and Sibley, L. D. ( 1999). Invasion by Toxoplasma gondii establishes a moving junction that selectively excludes host cell plasma membrane proteins on the basis of their membrane anchoring. Journal of Experimental Medicine 190, 1783–1792.CrossRefGoogle Scholar
Mordue, D. G. and Sibley, L. D. ( 1997). Intracellular fate of vacuoles containing Toxoplasma gondii is determined at the time of formation and depends on the mechanism of entry. Journal of Immunology 159, 4452–4459.Google Scholar
Naguleswaran, A., Alaeddine, F., Guionaud, C., Vonlaufen, N., Sonda, S., Jenoe, P., Mevissen, M. and Hemphill, A. ( 2005). Neospora caninum protein disulfide isomerase is involved in tachyzoite-host cell interaction. International Journal for Parasitology 35, 1459–1472.CrossRefGoogle Scholar
Naguleswaran, A., Cannas, A., Keller, N., Vonlaufen, N., Björkman, C. and Hemphill, A. ( 2002). Vero cell surface proteoglycan interaction with the microneme protein NcMIC3 mediates adhesion of Neospora caninum tachyzoites to host cells unlike that in Toxoplasma gondii. International Journal for Parasitology 32, 695–704.CrossRefGoogle Scholar
Naguleswaran, A., Cannas, A., Keller, N., Vonlaufen, N., Schares, G., Conraths, F. J., Björkman, C. and Hemphill, A. ( 2001). Neospora caninum microneme protein NcMIC3: Secretion, subcellular localization and functional involvement in host cell interaction. Infection and Immunity 69, 6483–6494.CrossRefGoogle Scholar
Naguleswaran, A., Müller, N. and Hemphill, A. ( 2003). Neospora caninum and Toxoplasma gondii: a novel adhesion/invasion assay reveals distinct differences in tachyzoite-host cell interactions. Experimental Parasitology 104, 149–158.CrossRefGoogle Scholar
Nishikawa, Y., Inoue, N., Xuan, X., Nagasawa, H., Igarasha, I., Fujisaka, K., Otsuka, H. and Mikami, T. ( 2001 a). Protective vaccination by recombinant vaccinia virus against Neospora caninum infection. Vaccine 19, 1381–1390.Google Scholar
Nishikawa, Y., Xuan, X., Nagasawa, H., Igarashi, I., Fujisaki, K., Otsuka, H. and Mikami, T. ( 2001 b). Prevention of vertical transmission of Neospora caninum in BALB/c mice by recombinant vaccinia virus carrying NcSRS2 gene. Vaccine 19, 1710–1716.Google Scholar
Nishikawa, Y., Mishima, M., Nagasawa, H., Igarashi, I., Fujisaki, K., Otsuka, H. and Mikami, T. ( 2001 c). Interferon gamma induced apoptosis in host cells infected with Neospora caninum. Parasitology 123, 25–31.Google Scholar
Nishikawa, Y., Makala, L., Otsuka, H., Mikami, T. and Nagasawa, H. ( 2002). Mechanisms of apoptosis in murine fibroblasts by two intracellular protozoan parasites, Toxoplasma gondii and Neospora caninum. Parasite Immunology 24, 347–354.CrossRefGoogle Scholar
Nishikawa, Y., Xuan, X., Nagasawa, H., Igarashi, I., Fujisaki, K., Otsuka, H. and Mikami, T. ( 2000). Monoclonal antibody inhibition of Neospora caninum tachyzoite invasion into host cells. International Journal for Parasitology 30, 51–58.CrossRefGoogle Scholar
Omata, Y., Kano, R., Masukata, Y., Kobayashi, Y., Igarashi, M., Maeda, R. and Saito, R. ( 2005). Development of Neospora caninum cultured with human serum in vitro and in vivo. Journal of Parasitology 91, 222–225.CrossRefGoogle Scholar
Opitz, C. and Soldati, D. ( 2002). ‘The glideosome’: a dynamic complex powering gliding motion and host cell invasion by Toxoplasma gondii. Molecular Microbiology 45, 597–604.CrossRefGoogle Scholar
Paré, J., Thurmond, M. C. and Hietala, S. K. ( 1996). Congenital Neospora caninum infection in dairy cattle and associated calfhood mortality. Canadian Journal of Veterinary Research 60, 133–139.Google Scholar
Peters, M., Lütkefels, E., Heckeroth, A. R. and Schares, G. ( 2001). Immunohistochemical and ultrastructural evidence for Neospora caninum tissue cysts in skeletal muscles of naturally infected dogs and cattle. International Journal for Parasitology 31, 1144–1148.CrossRefGoogle Scholar
Petersen, E., Lebech, M., Jensen, L., Lind, P., Rask, M., Bagger, P., bjorkman, C. and Uggla, A. ( 1999). Neospora caninum infection and repeated abortions in humans. Emerging Infectious Diseases 5, 278–280.CrossRefGoogle Scholar
Pinitkiatisakul, S., Mattsson, J. G., Wikman, M., Friedman, M., Bengtsson, K. L., Stahl, S. and Lunden, A. ( 2005). Immunization of mice against neosporosis with recombinant NcSRS2 iscoms. Veterinary Parasitology 129, 25–34.CrossRefGoogle Scholar
Purner, M. B., Berens, P. B., Nash, P. B., van Linden, A., Ross, E., Kruse, C., Krug, E. C. and Cureil, T. J. ( 1996). CD4-mediated and CD8-mediated cytotoxic and proliferative immune responses to Toxoplasma gondii in seropositive humans. Infection and Immunity 64, 4330–4338.Google Scholar
Quinn, H. E., Ellis, J. T. and Smith, N. C. ( 2002). Neospora caninum: a cause of immune-mediated failure of pregnancy? Trends in Parasitology 18, 391–394.Google Scholar
Quinn, H. E., Miller, C. M. and Ellis, J. T. ( 2004). The cell-mediated immune response to Neospora caninum during pregnancy in the mouse is associated with a bias towards production of interleukin-4. International Journal for Parasitology 34, 723–732.CrossRefGoogle Scholar
Rettigner, C., De Meerschman, F., Focant, C., Vanderplasschen, A. and Losson, B. ( 2004). The vertical transmission following the reactivation of a Neospora caninum chronic infection does not seem to be due to an alteration of the systemic immune response in pregnant CBA/Ca mice. Parasitology 128, 149–160.CrossRefGoogle Scholar
Risco-Castillo, V., Fernandez-Garcia, A. and Ortega-Mora, L. M. ( 2004). Comparative analysis of stress agents in a simplified in vitro system of Neospora caninum bradyzoite production. Journal of Parasitology 90, 466–470.CrossRefGoogle Scholar
Ritter, D. M., Kerlin, R., Sibert, G. and Brake, D. ( 2002). Immune factors influencing the course of infection with Neospora caninum in the murine host. Journal of Parasitology 88, 271–280.CrossRefGoogle Scholar
Romero, J. J., Perez, E. and Frankena, K. ( 2004). Effect of a killed whole Neospora caninum tachyzoite vaccine on the crude abotion rate of Costa Rican dairy cows under field conditions. Veterinary Parasitology 123, 149–159.CrossRefGoogle Scholar
Schares, G., Peters, M., Wurm, R., Barwald, A. and Conraths, F. J. ( 1998). The efficiency of vertical transmission of Neospora caninuim in dairy cattle analysed by serological techniques. Veterinary Parasitology 80, 87–98.CrossRefGoogle Scholar
Schares, G., Zinecker, C. F., Schmidt, J., Azzouz, N., Conraths, F. J., Gerold, P. and Schwarz, R. T. ( 2000). Structural analysis of free and protein-bound glycosyl-phosphatidylinositols of Neospora caninum. Molecular and Biochemical Parasitology 105, 155–161.CrossRefGoogle Scholar
Sher, A., Denkers, E. Y. and Gazzinelli, R. T. ( 1995). Induction and regulation of host cell mediated immunity by Toxoplasma gondii. Ciba Foundation Symposium 195, 95–104.Google Scholar
Shibahara, T., Kokuho, T., Eto, M., Haritani, M., Hamaoka, T., Shimura, K., Nakamura, K., Yokomizo, Y. and Yamane, I. ( 1999). Pathological and immunological findings of athymic nude and congenic wild type BALB/c mice experimentally infected with Neospora caninum. Veterinary Pathology 36, 321–327.CrossRefGoogle Scholar
Sinai, A. P. and Joiner, K. ( 2001). The Toxoplasma gondii protein ROP2 mediates host organelle association with the parasitophorous vacuole membrane. Journal of Cell Biology 154, 95–108.CrossRefGoogle Scholar
Sinai, A. P., Payne, T. M., Carmen, J. C., Hardi, L., Watson, S. J. and Molestina, R. E. ( 2004). Mechanisms underlying the manipulation of host apoptotic pathways by Toxoplasma gondii. International Journal for Parasitology 34, 381–391.CrossRefGoogle Scholar
Sinai, A. P., Webster, P. and Joiner, K. ( 1997). Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane: a high affinity interaction. Journal of Cell Science 110, 2117–2128.Google Scholar
Soete, M., Camus, D. and Dubremetz, J. F. ( 1994). Experimental induction of bradyzoite-specific antigen expression and cyst formation by the RH strain of Toxoplasma gondii in vitro. Experimental Parasitology 78, 361–370.CrossRefGoogle Scholar
Soldati, D., Dubremetz, J. F. and Lebrun, M. ( 2001). Microneme proteins: structural and functional requirements to promote adhesion and invasion by the apicomplexan parasite Toxoplasma gondii. International Journal for Parasitology 31, 1293–1302.CrossRefGoogle Scholar
Sonda, S., Fuchs, N., Connolly, B., Fernandez, P., Gottstein, B. and Hemphill, A. ( 1998). The major 36 kDa Neospora caninum tachyzoite surface protein is closely related to the major Toxoplasma gondii surface antigen 1. Molecular and Biochemical Parasitology 97, 97–108.CrossRefGoogle Scholar
Sonda, S., Fuchs, N., Gottstein, B. and Hemphill, A. ( 2000). Molecular characterization of a novel microneme antigen in Neospora caninum. Molecular and Biochemical Parasitology 108, 39–51.CrossRefGoogle Scholar
Speer, C. A., Dubey, J. P., McAllister, M. M. and Blixt, J. A. ( 1999). Comparative ultrastructure of tachyzoites, bradyzoites, and tissue cysts of Neospora caninum and Toxoplasma gondii. International Journal for Parasitology 29, 1509–1519.CrossRefGoogle Scholar
Staska, L. M., Dvies, C., Brown, W. C., McGuire, T. C., Suarez, C. E., Park, J. Y., Mathison, B. A., Abbott, J. R. and Baszler, T. V. ( 2005). Identification of vaccine candidate peptides in the NcSRS2 surface protein of Neospora caninum by using CD4+ cytotoxic T lymphocytes and gamma interferon secreting T lymphocytes of infected Holstein cattle. Infection and Immunity 73, 1321–1329.CrossRefGoogle Scholar
Staska, L. M., McGuire, T. C., Davies, C. J., Lewin, H. A. and Baszler, T. V. ( 2003). Neospora caninum infected cattle develop parasite specific CD4+ cytotoxic T lymphocytes. Infection and Immunity 71, 3272–3279.CrossRefGoogle Scholar
Stenlund, S., Bjorkman, C., Holmdahl, O. J., Kindahl, H. and Uggla, A. ( 1997). Characterization of a Swedish bovine isolate of Neospora caninum. Parasitology Research 83, 214–219.CrossRefGoogle Scholar
Tenter, A. M. and Johnson, A. M. ( 1997). Phylogeny of the tissue cyst-forming coccidian. Advances in Parasitology 39, 169–139.Google Scholar
Tomley, F. M. and Soldati, D. S. ( 2001). Mix and match modules: structure and function of microneme proteins in apicomplexan parasites. Trends in Parasitology 17, 81–88.CrossRefGoogle Scholar
Tranas, J., Heinzen, R. A., Weiss, L. M. and McAllister, M. M. ( 1999). Serological evidence of human infection with the protozoan Neospora caninum. Clinical and Diagnostic Laboratory Immunology 6, 765–777.Google Scholar
Trees, A. J., McAllister, M. M., Guy, C. S., McGarry, J. W., Smith, R. F. and Williams, D. J. ( 2002). Neospora caninum: oocyst challenge of pregnant cows. Veterinary Parasitology 109, 147–154.CrossRefGoogle Scholar
Tunev, S. S., McAllister, M. M., Anderson-Sprecher, R. C. and Weiss, L. M. ( 2002). Neospora caninumin vitro: evidence that the destiny of a parasitophorous vacuole depends on the phenotype of the progenitor zoite. Journal of Parasitology 88, 1095–1099.CrossRefGoogle Scholar
Tuo, W., Davis, W. C., Fetterer, R., Jenkins, M., Boyd, P. C., Gasbarre, L. C. and Dubey, J. P. ( 2004). Establishment of Neospora antigen-specific T cell lines of primarily CD4 T cells. Parasite Immunology 26, 243–246.CrossRefGoogle Scholar
Tuo, W., Fetterer, R. H., Davis, W. C., Jenkins, M. C. and Dubey, J. P. ( 2005). Neospora antigens defined by antigen-dependent bovine CD4+ T cells. Journal of Parasitology 91, 564–568.CrossRefGoogle Scholar
Uchida, Y., Ike, K., Kurotaki, T., Ito, A. and Imai, S. ( 2004). Monoclonal antibodies preventing invasion of Neospora caninum tachyzoites into host cells. Journal of Veterinary Medical Science 66, 1355–1358.CrossRefGoogle Scholar
Uggla, A., Stenlund, S., Holmdahl, O. J. M., Jakubek, E. B., Thebo, P., Kindahl, H. and Björkman, C. ( 1998). Oral Neospora caninum inoculation of neonatal calves. International Journal for Parasitology 28, 1467–1472.CrossRefGoogle Scholar
Vonlaufen, N., Guetg, N., Naguleswaran, A., Müller, N., Bjorkman, C., Schares, G., von Blumroeder, D., Ellis, J. and Hemphill, A. ( 2004). In vitro induction of Neospora caninum bradyzoites in Vero cells reveals differential antigen expression, localization, and host-cell recognition of tachyzoites and bradyzoites. Infection and Immunity 72, 576–583.CrossRefGoogle Scholar
Vonlaufen, N., Müller, N., Keller, N., Naguleswaran, A., Bohne, W., McAllister, M., Björkman, C., Müller, E., Caldelari, R. and Hemphill, A. ( 2002). Exogenous nitric oxide triggers Neospora caninum tachyzoite-to-bradyzoite stage conversion in murine epidermal keratinocyte cell cultures. International Journal for Parasitology 32, 1253–1265.CrossRefGoogle Scholar
Weiss, L. M., Ma, Y. F., Halonen, S., McAllister, M. M. and Zhang, Y. W. ( 1999). The in vitro development of Neospora caninum bradyzoites. International Journal for Parasitology 29, 1713–1723.CrossRefGoogle Scholar
Williams, D. J., Guy, C. S., Smith, R. F., Guy, F., McGarry, J. W., McKay, J. S. and Trees, A. J. ( 2003). First demonstration of protective immunity against foetopathy in cattle with latent Neospora caninum infection. International Journal for Parasitology 33, 1059–1065.CrossRefGoogle Scholar
Williams, D. J., Guy, C. S., McGarry, J. W., Guy, F., Tasker, L., Smith, R. F., MacEachern, K., Cripps, P. J., Kelly, D. F. and Trees, A. J. ( 2000). Neospora caninum-associated abortion in cattle: the time of experimentally-induced parasitaemia during gestation determines foetal survival. Parasitology 121, 347–358.CrossRefGoogle Scholar
Williams, D. J. and Trees, A. J. ( 2006). Protecting babies: vaccine strategies to prevent foetopathy in Neospora-infected cattle. Parasite Immunology 28, 61–67.CrossRefGoogle Scholar
Wouda, W., Bartels, C. J. M. and Moen, A. R. ( 1999). Characteristics of Neospora caninum associated abortion strorms in dairy herds in the Netherlands (1995–1997). Theriogenology 52, 233–245.CrossRefGoogle Scholar
Yamage, M., Flechtner, O. and Gottstein, B. ( 1996). Neospora caninum: specific oligonucleotide primers for the detection of brain “cyst” DNA of experimentally infected nude mice by the polymerase chain reaction (PCR). Journal of Parasitology 82, 272–279.CrossRefGoogle Scholar