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Pathological and immunological findings in placentas from pregnant BALB/c mice infected with Neospora caninum at early and late stages of gestation

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Abstract

Neospora caninum is transmitted from a cow to its foetus by vertical transmission and the timing of infection in gestation is an important factor in determining the disease outcome. Few studies have explored the role of the placenta in the outcome of N. caninum infection during pregnancy. Here, we described the N. caninum presence, parasite load, local immune response, and histopathological lesions at the materno-foetal interface after infection of BALB/c mice at early and late stages of gestation. In mice infected at early gestation, N. caninum DNA was detected in foetoplacentary units 7 days post-infection (PI) and in the placenta, but not in viable foetuses on day 14 PI, indicating that the parasite was multiplying primarily in the placental tissues without reaching the foetus. Moreover, parasite DNA was detected in resorptions, suggesting that foetal death could be a consequence of infection. An increase in IFN-γ, TNF-α and IL-10 expression was observed in N. caninum PCR-positive placentas, which could favour N. caninum foetal transmission and be harmful to both the placenta and the foetus. Histopathological analysis revealed necrosis affecting both the maternal and foetal sides of the placenta. At late gestation, transmission occurred rapidly following infection (day 3 PI), but parasite were rarely found. In addition, an increase in cytokine expression was observed in spleen and placental tissues from infected animals, while a downregulation in IL-4 expression was only observed in the spleen. Finally, necrosis in the placenta was limited to the maternal side, suggesting that the parasite is mainly multiplying in the placental tissue at this stage. Thus, the results of the present study indicate that the placenta may be actively involved in N. caninum pathogenesis.

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References

  • Abou-Bacar A., Pfaff A.W., Georges S., Letscher-Bru V., Filisetti D., Villard O., Antoni E., Klein J.P., Candolfi E. 2004. 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. DOI: 10.1128/IAI. 72.3.1397-1401.2004.

    Article  PubMed  CAS  Google Scholar 

  • Amarante-Paffaro A., Queiroz G.S., Corrêa S.T., Spira B., Bevilacqua E. 2004. Phagocytosis as a potential mechanism for microbial defense of mouse placental trophoblast cells. Reproduction, 128, 207–218. DOI: 10.1530/rep.1.00214.

    Article  PubMed  CAS  Google Scholar 

  • Barbosa B.F., Silva D.A., Costa I.N., Mineo J.R., Ferro E.A. 2008. BeWo trophoblast cell susceptibility to Toxoplasma gondii is increased by interferon-gamma, interleukin-10 and transforming growth factor-beta 1. Clinical and Experimental Immunology, 151, 536–545. DOI: 10.1111/j.1365-2249.2007.03583.x.

    Article  PubMed  CAS  Google Scholar 

  • Barr B.C., Rowe J.D., Sverlow S.K., BonDurant R.H., Ardans A.A., Oliver M.N., Conrad P.A. 1994. Experimental reproduction of bovine fetal Neospora infection and death with a bovine Neospora isolate. Journal of Veterinary Diagnostic Investigation, 6, 207–215.

    Article  PubMed  CAS  Google Scholar 

  • Buendía A.J., Sánchez J., Martínez M.C., Cámara P., Navarro J.A., Rodolakis A., Salinas J. 1998. Kinetics of infection and effects on placental cell populations in a murine model of Chlamydia psittaci-induced abortion. Infection and Immunity, 66, 2128–2134.

    PubMed  Google Scholar 

  • Buxton D., Maley S.W., Wright S., Thomson K.M., Rae A.G., Innes E.A. 1998. The pathogenesis of experimental neosporosis in pregnant sheep. Journal of Comparative Pathology, 118, 267–279. DOI: 10.1016/S0021-9975(07)80003-X.

    Article  PubMed  CAS  Google Scholar 

  • Chaouat G., Menu E., Clark D.A., Dy M., Minkowski M., Wegmann T.G. 1990. Control of fetal survival in CBA × DBA/2 mice by lymphokine therapy. Journal of Reproduction and Fertility, 89, 447–458. DOI: 10.1530/jrf.0.0890447.

    Article  PubMed  CAS  Google Scholar 

  • Cole R.A., Lindsay D.S., Blagburn B.L., Dubey J.P. 1995. Vertical transmission of Neospora caninum in mice. Journal of Parasitology, 81, 730–732. DOI: 10.2307/3283962.

    Article  PubMed  CAS  Google Scholar 

  • Collantes-Fernández E., RodrÍguez-Bertos A., Arnaiz-Seco I., Moreno B., Aduriz G., Ortega-Mora L.M. 2006. Influence of the stage of pregnancy on Neospora caninum distribution, parasite loads and lesions in aborted bovine foetuses. Theriogenology, 65, 629–641. DOI: 10.1016/j.theriogenology.2005.06.003.

    Article  PubMed  Google Scholar 

  • Collantes-Fernández E., Zaballos Á., Álvarez-García G., Ortega-Mora L.M. 2002. Quantitative detection of Neospora caninum in bovine aborted fetuses and experimentally infected mice by real-time PCR. Journal of Clinical Microbiology, 40, 1194–1198. DOI: 10.1128/JCM.40.4.1194-1198.2002.

    Article  PubMed  Google Scholar 

  • Dubey J.P., Buxton D., Wouda W. 2006. Pathogenesis of bovine neosporosis. Journal of Comparative Pathology, 134, 267–289. DOI: 10.1016/j.jcpa.2005.11.004.

    Article  PubMed  CAS  Google Scholar 

  • Dubey J.P., Lindsay D.S. 1996. A review of Neospora caninum and neosporosis. Veterinary Parasitology, 67, 1–59. DOI: 10.1016/S0304-4017(96)01035-7.

    Article  PubMed  CAS  Google Scholar 

  • Dubey J.P., Lindsay D.S., Anderson M.L., Davis S.W., Shen S.K. 1992. Induced transplacental transmission of Neospora caninum in cattle. Journal of the American Veterinary Medical Association, 201, 709–713.

    PubMed  CAS  Google Scholar 

  • Eperon S., Brönnimann K., Hemphill A., Gottstein B. 1999. Susceptibility of B-cell deficient C57BL/6 (μMT) mice to Neospora caninum infection. Parasite Immunology, 21, 225–236. DOI: 10.1046/j.1365-3024.1999.00223.x.

    Article  PubMed  CAS  Google Scholar 

  • Ferro E.A., Silva D.A., Bevilacqua E., 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. DOI: 10.1128/IAI.70.12.7089-7094.2002.

    Article  PubMed  CAS  Google Scholar 

  • Innes E.A., Andrianarivo A.G., Björkman C., Williams D.J., Conrad P.A. 2002. Immune responses to Neospora caninum and prospects for vaccination. Trends in Parasitology, 18, 497–504. DOI: 10.1016/S1471-4922(02)02372-3.

    Article  PubMed  CAS  Google Scholar 

  • Innes 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. International Journal for Parasitology, 31, 1523–1534. DOI: 10.1016/S0020-7519(01)00284-3.

    Article  PubMed  CAS  Google Scholar 

  • Kano R., Masukata Y., Omata Y., Kobayashi Y., Maeda R., 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. DOI: 10.1016/j.vetpar.2005.01.004.

    Article  PubMed  CAS  Google Scholar 

  • Krishnan L., Guilbert L.J., Wegmann T.G., Belosevic M., Mosmann T.R. 1996. T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells. Journal of Immunology, 156, 653–662.

    CAS  Google Scholar 

  • Liddell S., Jenkins M.C., Dubey J.P. 1999. Vertical transmission of Neospora caninum in BALB/c mice determined by polymerase chain reaction detection. Journal of Parasitology, 85, 550–555. DOI: 10.2307/3285794.

    PubMed  CAS  Google Scholar 

  • Lin H., Mosmann T.R., Guilbert L., Tuntipopipat S., Wegmann T.G. 1993. Synthesis of T helper 2-type cytokines at the maternalfetal interface. Journal of Immunology, 151, 4562–4573.

    CAS  Google Scholar 

  • Livak K., Schmittgen T.D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 25, 402–408. DOI: 10.1006/meth.2001.1262.

    Article  PubMed  CAS  Google Scholar 

  • Long M.T., Baszler T.V. 1996. Fetal loss in BALB/c mice infected with Neospora caninum. Journal of Parasitology, 82, 608–611. DOI: 10.2307/3283785.

    Article  PubMed  CAS  Google Scholar 

  • Long M.T., 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.

    CAS  Google Scholar 

  • López-Pérez I.C., Collantes-Fernández E., Aguado-MartÍnez A., Rodríguez-Bertos A., Ortega-Mora L.M. 2008. Influence of Neospora caninum infection in BALB/c mice during preg nancy in post-natal development. Veterinary Parasitology, 155, 175–183. DOI: 10.1016/j.vetpar.2008.05.018.

    Article  PubMed  Google Scholar 

  • López-Pérez I.C., Collantes-Fernández E., Rojo-Montejo S., Navarro-Lozano V., Risco-Castillo V., Pérez-Pérez V., Pereira-Bueno J., Ortega-Mora L.M. 2010. Effects of Neospora caninum infection at mid-gestation on placenta in a pregnant mouse model. Journal of Parasitology, 96, 1017–1020. DOI: 10.1645/GE-2347.1.

    Article  PubMed  Google Scholar 

  • López-Pérez I., Risco-Castillo V., Collantes-Fernández E., Ortega-Mora L.M. 2006. Comparative effect of infection with Neospora caninum at the three gestation periods. Journal of Parasitology, 92, 1286–1291. DOI: 10.1645/GE-883R.1.

    Article  PubMed  Google Scholar 

  • Macaldowie C., Maley S.W., Wright S., Bartley P., Esteban-Redondo 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. Journal of Comparative Pathology, 131, 142–156. DOI: 10.1016/j.jcpa. 2004.02.005.

    Article  PubMed  CAS  Google Scholar 

  • Maley 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. Journal of Comparative Pathology, 135, 130–141. DOI: 10.1016/j.jcpa. 2006.07.001

    Article  PubMed  CAS  Google Scholar 

  • Maley 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. 2003. The pathogenesis of neosporosis in pregnant cattle: inoculation at mid-gestation. Journal of Comparative Pathology, 129, 186–195. DOI: 10.1016/S0021-9975 (03)00032-X.

    Article  PubMed  CAS  Google Scholar 

  • Moormann A.M., Sullivan D., Rochford R.A., Chensue S.W., Bock P.J., Nyirenda T., Meshnick S.R. 1999. Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation. Journal of Infectious Diseases, 180, 1987–1993. DOI: 10.1086/315135.

    Article  PubMed  CAS  Google Scholar 

  • Morrison D. 2002. How to improve statistical analysis in parasitology research publications. International Journal for Parasitology, 32, 1065–1070. DOI:10.1016/S0020-7519(02)000 64-4.

    Article  PubMed  Google Scholar 

  • Ohmori Y., Hamilton T.A. 1997. IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages. Journal of Immunology, 159, 5474–5482.

    CAS  Google Scholar 

  • Omata Y., Nidaira M., Kano R., Kobayashi Y., Koyama T., Furuoka H., Maeda R., Matsui T., Saito A. 2004. Vertical transmission of Neospora caninum in BALB/c mice in both acute and chronic infection. Veterinary Parasitology, 121, 323–328. DOI: 10.1016/j.vetpar.2004.03.003.

    Article  PubMed  CAS  Google Scholar 

  • Pereira-Bueno J., Quintanilla-Gozalo A., Pérez-Pérez V., Espi-Felgueroso A., álvarez-GarcÍa G., Collantes-Fernández E., Ortega-Mora L.M. 2003. Evaluation by different diagnostic techniques of bovine abortion associated with Neospora caninum in Spain. Veterinary Parasitology, 111, 143–152. DOI: 10.1016/S0304-4017(02)00361-8.

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Zaballos F.J., Ortega-Mora L.M., álvarez-GarcÍa G., Collantes-Fernández E., Navarro-Lozano V., GarcÍa-Villada L., Costas E. 2005. Adaptation of Neospora caninum isolates to cell-culture changes: an argument in favor of its clonal population structure. Journal of Parasitology, 91, 507–510. DOI: 10.1645/GE-381R1.

    Article  PubMed  Google Scholar 

  • Pfaff A.W., Villard O., Klein J.P., Mousli M., Candolfi E. 2005. 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. DOI: 10.1016/j.ijpara.2005.08.003.

    Article  PubMed  CAS  Google Scholar 

  • Quinn H.E., Ellis J.T., Smith N.C. 2002a. Neospora caninum: a cause of immune-mediated failure of pregnancy? Trends in Parasitology, 18, 391–394. DOI: 10.1016/S1471-4922(02)02324-3.

    Article  PubMed  CAS  Google Scholar 

  • Quinn H.E., Miller C.M., 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. DOI: 10.1016/j.ijpara.2004.01.007.

    Article  PubMed  CAS  Google Scholar 

  • Quinn H.E., Miller C.M., Ryce C., Windsor P.A., Ellis J.T. 2002b. Characterization of an outbred pregnant mouse model of Neospora caninum infection. Journal of Parasitology, 88, 691–696. DOI: 10.2307/3285344.

    Article  PubMed  Google Scholar 

  • Raghupathy R. 1997. Th1-type immunity is incompatible with successful pregnancy. Immunology Today, 18, 478–482. DOI: 10.1016/S0167-5699(97)01127-4.

    Article  PubMed  CAS  Google Scholar 

  • Rosbottom A., Gibney E.H., Guy C.S., Kipar A., Smith R.F., Kaiser P., Trees A.J., Williams D.J. 2008. An upregulation of cytokines is detected in the placentas of cattle infected with Neospora caninum and is more marked early in gestation when fetal death is observed. Infection and Immunity, 76, 2352–2361. DOI: 10.1128/IAI.01780-06.

    Article  PubMed  CAS  Google Scholar 

  • Rosbottom A., Gibney E.H., Kaiser C., Smith R.F., Robinson R., Kipar A., Williams D.J. 2011. Up regulation of the maternal immune response in the placenta of cattle naturally infected with Neospora caninum. PLoS One, 6, e15799. DOI: 10.1371/journal.pone.0015799.

    Article  PubMed  CAS  Google Scholar 

  • Trees A.J., Williams D.J.L. 2005. Endogenous and exogenous transplacental infection in Neospora caninum and Toxoplasma gondii. Trends in Parasitology, 21, 558–561. DOI: 10.1016/j.pt.2005.09.005.

    Article  PubMed  Google Scholar 

  • Varona R., Cadenas V., Gómez L., MartÍnez A., Márquez G. 2005. CCR6 regulates CD4+ T-cell-mediated acute graft-versushost disease responses. Blood, 106, 18–26. DOI: 10.1182/blood-2004-08-2996.

    Article  PubMed  CAS  Google Scholar 

  • Wegmann T.G., Lin H., Guilbert L., Mosmann T.R. 1993. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a Th2 phenomenon? Immunology Today, 14, 353–356. DOI: 10.1016/0167-5699(93)90235-D.

    Article  PubMed  CAS  Google Scholar 

  • Whitten M.K. 1957. Effect of exteroceptive factors on the oestrous cycle of mice. Nature, 180(4599): 1436. DOI: 10.1038/1801436a0.

    Article  PubMed  CAS  Google 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., 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. DOI: 10.1017/S0031182099006587.

    Article  PubMed  Google Scholar 

  • Williams D.J., Guy C.S., Smith R.F., Guy F., McGarry J.W., McKay J.S., 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. DOI: 10.1016/S0020-7519(03)00143-7.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Saluvet Group, Animal Health Department, Veterinary Faculty, Complutense University of Madrid, Avenida Puerta de Hierro, s/n, 28040, Madrid, Spain

    Inmaculada C. López-Pérez, Esther Collantes-Fernández, Silvia Rojo-Montejo, Vanesa Navarro-Lozano, Verónica Risco-Castillo & Luis Miguel Ortega-Mora

  2. Animal Health Department, Veterinary Faculty, University of León, 24071, León, Spain

    Valentín Pérez-Pérez & Juana Pereira-Bueno

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  1. Inmaculada C. López-Pérez
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  2. Esther Collantes-Fernández
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  3. Silvia Rojo-Montejo
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  4. Vanesa Navarro-Lozano
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  5. Verónica Risco-Castillo
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  6. Valentín Pérez-Pérez
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  7. Juana Pereira-Bueno
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  8. Luis Miguel Ortega-Mora
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Correspondence to Luis Miguel Ortega-Mora.

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López-Pérez, I.C., Collantes-Fernández, E., Rojo-Montejo, S. et al. Pathological and immunological findings in placentas from pregnant BALB/c mice infected with Neospora caninum at early and late stages of gestation. Acta Parasit. 56, 245–254 (2011). https://doi.org/10.2478/s11686-011-0052-8

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