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dc.contributor.advisorDutia, Bernadette
dc.contributor.advisorInnes, Elisabeth A.
dc.contributor.advisorKatzer, Frank
dc.contributor.authorBartley, Paul Murdoch
dc.date.accessioned2017-09-22T14:49:41Z
dc.date.available2017-09-22T14:49:41Z
dc.date.issued2017-03-01
dc.identifier.urihttp://hdl.handle.net/1842/23592
dc.description.abstractThe papers included in this thesis examine the host–parasite relationship in small and large animals following experimental challenges with Neospora caninum. This apicomplexan parasite is a major cause of abortion and reproductive losses in cattle worldwide. Economic and welfare issues make the development of a vaccine against the transplacental transmission of Neospora highly desirable. This thesis evaluates the host-parasite interactions in a non-pregnant mouse model examining whether the actively multiplying stage of the parasite (tachyzoite) could be attenuated through prolonged in vitro cultivation (passage) and used as a live vaccine. We show that continued maintenance of tachyzoites in tissue culture produced significantly reduced levels of morbidity and mortality in the mice following challenge, compared to mice receiving virulent parasites. Inoculation with a sub-lethal dose of tachyzoites was shown to protect against a subsequent lethal challenge of virulent parasites. Mice showing higher levels of cell mediated immunity (CMI) (antigen-specific splenocyte proliferation and interferon-γ (IFN-γ) production) had lower parasite burdens compared to mice with less pronounced CMI responses. Combined, these works show that it is possible to protect against a lethal challenge using attenuated tachyzoites and that a strong T-helper Type-1 CMI response is involved in protection and in reducing clinical disease severity. As the most commonly known route of infection with N. caninum is transplacental, from dam to foetus, we also wanted to examine the host-parasite relationship in pregnant cattle. This was done through the serial examination of the maternal and foetal immune responses of experimentally challenged cattle under controlled conditions at different stages throughout pregnancy. These works show the importance of the timing, location and magnitude of multiple components of the host immune response in determining foetal survival and also whether vertical transmission occurs. We show that both the maternal and foetal immune responses are critical in determining the clinical outcome of infection. A strong maternal CMI response was shown to aid foetal survival by reducing the numbers of parasites reaching and thus damaging the placenta. Due to the syndesmychorial nature of the ruminant placenta, any foetal responses observed are as a result of foetal infection. These experiments show that as pregnancy progresses the foetus goes from being immunologically immature and incapable of mounting a protective immune response (70 days of gestation (dg)) to becoming capable of mounting parasite-specific humoral, innate and CMI responses from around 140dg onwards. The experiments in pregnant cattle confirm the importance of parasite-specific proliferation and IFN-γ production, in reducing the magnitude of the parasite challenge reaching the maternal–foetal interface and aiding foetal survival. We also examined the immunodominant parasite peptides expressed in HPLC fractionated tachyzoite antigen, which are recognised by the cellular immune response of experimentally challenged cattle. Through LC-ESI-MS/MS, 6 Neospora proteins (including SAG1, SRS2 and GRA2) and a number of Toxoplasma gondii orthologues were identified and found to be recognised by CD4+ T-cells. These works collectively demonstrate the complexity of the host-parasite interaction in Neospora infections and show the importance of a CMI response in protection against the parasite.en
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.relation.hasversionBARTLEY, P. M., KATZER, F., ROCCHI, M. S., MALEY, S. W., BENAVIDES, J., NATH, M., PANG, Y., CANTON, G., THOMSON, J., CHIANINI, F. & INNES, E. A. 2013a. Development of maternal and foetal immune responses in cattle following experimental challenge with Neospora caninum at day 210 of gestation. Vet Res, 44, 91.en
dc.relation.hasversionBARTLEY, P. M., KIRVAR, E., WRIGHT, S., SWALES, C., ESTEBANREDONDO, I., BUXTON, D., MALEY, S. W., SCHOCK, A., RAE, A. G., HAMILTON, C. & INNES, E. A. 2004. Maternal and fetal immune responses of cattle inoculated with Neospora caninum at mid-gestation. J Comp Pathol, 130, 81-91.en
dc.relation.hasversionBARTLEY, P. M., WRIGHT, S., CHIANINI, F., BUXTON, D. & INNES, E. A. 2008. Inoculation of Balb/c mice with live attenuated tachyzoites protects against a lethal challenge of Neospora caninum. Parasitology, 135, 13-21.en
dc.relation.hasversionBARTLEY, P. M., WRIGHT, S., SALES, J., CHIANINI, F., BUXTON, D. & INNES, E. A. 2006. Long-term passage of tachyzoites in tissue culture can attenuate virulence of Neospora caninum in vivo. Parasitology, 133, 421- 432.en
dc.relation.hasversionBARTLEY, P. M., WRIGHT, S. E., MALEY, S. W., BUXTON, D., NATH, M. & INNES, E. A. 2009. The development of immune responses in Balb/c mice following inoculation with attenuated or virulent Neospora caninum tachyzoites. Parasite Immunol, 31, 392-401.en
dc.relation.hasversionBARTLEY, P. M., WRIGHT, S. E., MALEY, S. W., MACALDOWIE, C. N., NATH, M., HAMILTON, C. M., KATZER, F., BUXTON, D. & INNES, E. A. 2012. Maternal and foetal immune responses of cattle following an experimental challenge with Neospora caninum at day 70 of gestation. Vet Res, 43, 38.en
dc.relation.hasversionBARTLEY, P. M., WRIGHT, S. E., ZIMMER, I. A., ROY, S., KITCHENER, A. C., MEREDITH, A., INNES, E. A. & KATZER, F. 2013b. Detection of Neospora caninum in wild carnivorans in Great Britain. Vet Parasitol, 192, 279-83.en
dc.relation.hasversionBENAVIDES, J., KATZER, F., MALEY, S. W., BARTLEY, P. M., CANTON, G., PALAREA-ALBALADEJO, J., PURSLOW, C. A., PANG, Y., ROCCHI, M. S., CHIANINI, F., BUXTON, D. & INNES, E. A. 2012. High rate of transplacental infection and transmission of Neospora caninum following experimental challenge of cattle at day 210 of gestation. Vet Res, 43, 83.en
dc.relation.hasversionBURRELLS, A., BENAVIDES, J., CANTON, G., GARCIA, J. L., BARTLEY, P. M., NATH, M., THOMSON, J., CHIANINI, F., INNES, E. A. & KATZER, F. 2015. Vaccination of pigs with the S48 strain of Toxoplasma gondii--safer meat for human consumption. Vet Res, 46, 47.en
dc.relation.hasversionBUXTON, D., MALEY, S. W., WRIGHT, S. E., RODGER, S., BARTLEY, P. & INNES, E. A. 2007. Toxoplasma gondii and ovine toxoplasmosis: new aspects of an old story. Vet Parasitol, 149, 25-8.en
dc.relation.hasversionCANTON, G. J., KATZER, F., BENAVIDES-SILVAN, J., MALEY, S. W., PALAREA-ALBALADEJO, J., PANG, Y., SMITH, S., BARTLEY, P. M., ROCCHI, M., INNES, E. A. & CHIANINI, F. 2013. Phenotypic characterisation of the cellular immune infiltrate in placentas of cattle following experimental inoculation with Neospora caninum in late gestation. Vet Res, 44, 60.en
dc.relation.hasversionCANTON, G. J., KATZER, F., MALEY, S. W., BARTLEY, P. M., BENAVIDESSILVAN, J., PALAREA-ALBALADEJO, J., PANG, Y., SMITH, S. H., ROCCHI, M., BUXTON, D., INNES, E. A. & CHIANINI, F. 2014a. Cytokine expression in the placenta of pregnant cattle after inoculation with Neospora caninum. Vet Immunol Immunopathol, 161, 77-89.en
dc.relation.hasversionCANTON, G. J., KATZER, F., MALEY, S. W., BARTLEY, P. M., BENAVIDESSILVAN, J., PALAREA-ALBALADEJO, J., PANG, Y., SMITH, S. H., ROCCHI, M. S., BUXTON, D., INNES, E. A. & CHIANINI, F. 2014. Inflammatory infiltration into placentas of Neospora caninum challenged cattle correlates with clinical outcome of pregnancy. Vet Res, 45, 11.en
dc.relation.hasversionINNES, E. A., BARTLEY, P. M., MALEY, S. W., WRIGHT, S. E. & BUXTON, D. 2007. Comparative host-parasite relationships in ovine toxoplasmosis and bovine neosporosis and strategies for vaccination. Vaccine, 25, 5495-503.en
dc.relation.hasversionINNES, E. A., BARTLEY, P. M., ROCCHI, M., BENAVIDAS-SILVAN, J., BURRELLS, A., HOTCHKISS, E., CHIANINI, F., CANTON, G. & KATZER, F. 2011. Developing vaccines to control protozoan parasites in ruminants: dead or alive? Vet Parasitol, 180, 155-63.en
dc.relation.hasversionINNES, E. A., WRIGHT, S. E., MALEY, S., RAE, A., SCHOCK, A., KIRVAR, E., BARTLEY, P., HAMILTON, C., CAREY, I. M. & BUXTON, D. 2001. Protection against vertical transmission in bovine neosporosis. Int J Parasitol, 31, 1523-34.en
dc.relation.hasversionMACALDOWIE, C., MALEY, S. W., WRIGHT, S., BARTLEY, P., ESTEBANREDONDO, I., BUXTON, D. & INNES, E. A. 2004. Placental pathology associated with fetal death in cattle inoculated with Neospora caninum by two different routes in early pregnancy. J Comp Pathol, 131, 142-56.en
dc.relation.hasversionMALEY, S. W., BUXTON, D., MACALDOWIE, C. N., ANDERSON, I. E., WRIGHT, S. E., BARTLEY, P. M., ESTEBAN-REDONDO, I., HAMILTON, C. M., STORSET, A. K. & INNES, E. A. 2006. Characterization of the immune response in the placenta of cattle experimentally infected with Neospora caninum in early gestation. J Comp Pathol, 135, 130-41.en
dc.relation.hasversionMALEY, S. W., BUXTON, D., RAE, A. G., WRIGHT, S. E., SCHOCK, A., BARTLEY, P. M., ESTEBAN-REDONDO, I., SWALES, C., HAMILTON, C. M., SALES, J. & INNES, E. A. 2003b. The pathogenesis of neosporosis in pregnant cattle: inoculation at mid-gestation. J.Comp.Pathol., 129, 186-195.en
dc.relation.hasversionROCCHI, M. S., BARTLEY, P. M., INGLIS, N. F., COLLANTES-FERNANDEZ, E., ENTRICAN, G., KATZER, F. & INNES, E. A. 2011. Selection of Neospora caninum antigens stimulating bovine CD4+ve T cell responses through immuno-potency screening and proteomic approaches. Vet Res, 42, 91.en
dc.subjectNeospora caninumen
dc.subjectcattleen
dc.subjectmice immunologyen
dc.titleHost-parasite interactions of Neospora caninumen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD(P) Doctor of Philosophy by Research Publicationsen


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