Influence of dose and route of administration on the outcome of infection with the virulent Neospora caninum isolate Nc-Spain7 in pregnant sheep at mid-gestation
Tóm tắt
Experimental infections in pregnant sheep have been focused on studying the effect of the time of challenge on the outcome of N. caninum infection, whereas the impact of the dose and route of challenge has not been studied in depth. Therefore, clinical outcome, immune responses, parasite detection and burden, and lesion severity in placental tissues and foetal brains were investigated in 90-day-pregnant sheep inoculated intravenously with 105 (G1), 104 (G2), 103 (G3), or 102 (G4) tachyzoites or subcutaneously with 104 (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6). Comparing challenge doses, G1 was the only group that had 100% abortion. Likewise, IFNγ levels in G1 increased earlier than those in other intravenously infected groups, and IgG levels on day 21 post-infection (pi) were higher in G1 than those in other intravenously infected groups. Concerning vertical transmission, G1 shows a higher parasite burden in the foetal brain than did G2 and G3. Comparing routes of administration, no differences in foetal survival rate or parasite load in the foetal brain were found. Although G2 had higher IFNγ levels than G5 on day 10 pi, no differences were found in humoral immune responses. Because the outcome after intravenous infection with 105 tachyzoites was similar to that observed after intravenous infection with 106 tachyzoites used in a previous work (100% abortion and vertical transmission), we conclude that it may be reasonable to use 105 tachyzoites administered by the intravenous route in further experiments when assessing drugs or vaccine candidates.
Tài liệu tham khảo
Dubey JP, Schares G, Ortega-Mora LM (2007) Epidemiology and control of neosporosis and Neospora caninum. Clin Microbiol Rev 20:323–367
Reichel MP, Alejandra Ayanegui-Alcérreca M, Gondim LFP, Ellis JT (2013) What is the global economic impact of Neospora caninum in cattle—the billion dollar question. Int J Parasitol 43:133–142
Dubey J, Hemphill A, Calero-Bernal R, Schares G (2017) Neosporosis in animals. CRC Press, Boca Ratón
Moreno B, Collantes-Fernandez E, Villa A, Navarro A, Regidor-Cerrillo J, Ortega-Mora LM (2012) Occurrence of Neospora caninum and Toxoplasma gondii infections in ovine and caprine abortions. Vet Parasitol 187:312–318
West DM, Pomroy WE, Collett MG, Hill FI, Ridler AL, Kenyon PR, Morris ST, Pattison RS (2006) A possible role for Neospora caninum in ovine abortion in New Zealand. Small Rumin Res 62:135–138
González-Warleta M, Castro-Hermida JA, Regidor-Cerrillo J, Benavides J, Alvarez-Garcia G, Fuertes M, Ortega-Mora LM, Mezo M (2014) Neospora caninum infection as a cause of reproductive failure in a sheep flock. Vet Res 45:88
McAllister MM, McGuire AM, Jolley WR, Lindsay DS, Trees AJ, Stobart RH (1996) Experimental neosporosis in pregnant ewes and their offspring. Vet Pathol 33:647–655
Arranz-Solis D, Benavides J, Regidor-Cerrillo J, Fuertes M, Ferre I, Ferreras Mdel C, Collantes-Fernandez E, Hemphill A, Perez V, Ortega-Mora LM (2015) Influence of the gestational stage on the clinical course, lesional development and parasite distribution in experimental ovine neosporosis. Vet Res 46:19
Weston JF, Howe L, Collett MG, Pattison RS, Williamson NB, West DM, Pomroy WE, Syed-Hussain SS, Morris ST, Kenyon PR (2009) Dose-titration challenge of young pregnant sheep with Neospora caninum tachyzoites. Vet Parasitol 164:183–191
Dubey J, Lindsay DS (1990) Neospora caninum induced abortion in sheep. J Vet Diagn Invest 2:230–233
Buxton D, Wright S, Maley SW, Rae AG, Lunden A, Innes EA (2001) Immunity to experimental neosporosis in pregnant sheep. Parasite Immunol 23:85–91
Innes EA, Lunden A, Esteban I, Marks J, Maley S, Wright S, Rae A, Harkins D, Vermeulen A, McKendrick IJ, Buxton D (2001) A previous infection with Toxoplasma gondii does not protect against a challenge with Neospora caninum in pregnant sheep. Parasite Immunol 23:121–132
Macaldowie C, Maley SW, Wright S, Bartley P, Esteban-Redondo I, Buxton D, Innes EA (2004) Placental pathology associated with fetal death in cattle inoculated with Neospora caninum by two different routes in early pregnancy. J Comp Pathol 131:142–156
Benavides J, Collantes-Fernandez E, Ferre I, Perez V, Campero C, Mota R, Innes E, Ortega-Mora LM (2014) Experimental ruminant models for bovine neosporosis: what is known and what is needed. Parasitology 141:1471–1488
Regidor-Cerrillo J, Gómez-Bautista M, Pereira-Bueno J, Adúriz G, Navarro-Lozano V, Risco-Castillo V, Fernández-García A, Pedraza-Díaz S, Ortega-Mora LM (2008) Isolation and genetic characterization of Neospora caninum from asymptomatic calves in Spain. Parasitology 135:1651–1659
Porto WJN, Regidor-Cerrillo J, Kim PCP, Benavides J, Silva ACS, Horcajo P, Oliveira AAF, Ferre I, Mota RA, Ortega-Mora LM (2016) Experimental caprine neosporosis: the influence of gestational stage on the outcome of infection. Vet Res 47:29
Caspe SG, Moore DP, Leunda MR, Cano DB, Lischinsky L, Regidor-Cerrillo J, Álvarez-García G, Echaide IG, Bacigalupe D, Ortega-Mora LM, Odeon AC, Campero CM (2012) The Neospora caninum-Spain 7 isolate induces placental damage, fetal death and abortion in cattle when inoculated in early gestation. Vet Parasitol 189:171–181
Regidor-Cerrillo J, Arranz-Solis D, Benavides J, Gomez-Bautista M, Castro-Hermida JA, Mezo M, Perez V, Ortega-Mora LM, Gonzalez-Warleta M (2014) Neospora caninum infection during early pregnancy in cattle: how the isolate influences infection dynamics, clinical outcome and peripheral and local immune responses. Vet Res 45:10
Almería S, Serrano-Perez B, Darwich L, Domingo M, Mur-Novales R, Regidor-Cerrillo J, Cabezón O, Pérez-Maillo M, Lopez-Helguera I, Fernández-Aguilar X (2016) Foetal death in naive heifers inoculated with Neospora caninum isolate Nc-Spain7 at 110 days of pregnancy. Exp Parasitol 168:62–69
Abecia JA, Forcada F, González-Bulnes A (2011) Pharmaceutical control of reproduction in sheep and goats. Vet Clin of North Am Food Anim Pract 27:67–79
Regidor-Cerrillo J, Gómez-Bautista M, Del Pozo I, Jiménez-Ruiz E, Aduriz G, Ortega-Mora LM (2010) Influence of Neospora caninum intra-specific variability in the outcome of infection in a pregnant BALB/c mouse model. Vet Res 41:52
Diffay BC, McKenzie D, Wolf C, Pugh DG (2002) Handling and examination of sheep and goats. In: Pugh DG (ed) Sheep and goat medicine. WB Saunders Company, Philadelphia
Sánchez-Sánchez R, Ferre I, Re M, Vázquez P, Ferrer LM, Blanco-Murcia J, Regidor-Cerrillo J, Díaz MP, González-Huecas M, Tabanera E (2018) Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites. Int J Parasitol Drugs Drug Resist 8:112–124
Alvarez-García G, Collantes-Fernandez E, Costas E, Rebordosa X, Ortega-Mora LM (2003) Influence of age and purpose for testing on the cut-off selection of serological methods in bovine neosporosis. Vet Res 34:341–352
Buxton D (1998) Protozoan infections (Toxoplasma gondii, Neospora caninum and Sarcocystis spp.) in sheep and goats: recent advances. Vet Res 29:289–310
Collantes-Fernández E, Zaballos A, Álvarez-García G, Ortega-Mora LM (2002) Quantitative detection of Neospora caninum in bovine aborted fetuses and experimentally infected mice by real-time PCR. J Clin Microbiol 40:1194–1198
Gutiérrez J, O’Donovan J, Proctor A, Brady C, Marques PX, Worrall S, Nally JE, McElroy M, Bassett H, Fagan J, Maley S, Buxton D, Sammin D, Markey BK (2012) Application of quantitative real-time polymerase chain reaction for the diagnosis of toxoplasmosis and enzootic abortion of ewes. J Vet Diagn Invest 24:846–854
Buxton D, Maley SW, Wright S, Thomson KM, Rae AG, Innes EA (1998) The pathogenesis of experimental neosporosis in pregnant sheep. J Comp Pathol 118:267–279
Dubey JP, Buxton D, Wouda W (2006) Pathogenesis of bovine neosporosis. J Comp Pathol 134:267–289
Buxton D, Maley SW, Thomson KM, Trees AJ, Innes EA (1997) Experimental infection of non-pregnant and pregnant sheep with Neospora caninum. J Comp Pathol 117:1–16
Gardner DS, Buttery PJ, Daniel Z, Symonds ME (2007) Factors affecting birth weight in sheep: maternal environment. Reproduction 133:297–307
Maley SW, Buxton D, Thomson KM, Schriefer CE, Innes EA (2001) Serological analysis of calves experimentally infected with Neospora caninum: a 1-year study. Vet Parasitol 96:1–9
Maley SW, Buxton D, Rae AG, Wright SE, Schock A, Bartley PM, Esteban-Redondo I, Swales C, Hamilton CM, Sales J, Innes EA (2003) The pathogenesis of neosporosis in pregnant cattle: inoculation at mid-gestation. J Comp Pathol 129:186–195
Benavides J, Katzer F, Maley SW, Bartley PM, Canton G, Palarea-Albaladejo J, Purslow CA, Pang Y, Rocchi MS, Chianini F, Buxton D, Innes EA (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
Almería S, Araujo R, Tuo W, López-Gatius F, Dubey JP, Gasbarre LC (2010) Fetal death in cows experimentally infected with Neospora caninum at 110 days of gestation. Vet Parasitol 168:62–69
Wiengcharoen J, Thompson RC, Nakthong C, Rattanakorn P, Sukthana Y (2011) Transplacental transmission in cattle: is Toxoplasma gondii less potent than Neospora caninum? Parasitol Res 108:1235–1241
Rocchi MS, Bartley PM, Inglis NF, Collantes-Fernandez E, Entrican G, Katzer F, Innes EA (2011) Selection of Neospora caninum antigens stimulating bovine CD4+ ve T cell responses through immuno-potency screening and proteomic approaches. Vet Res 42:91
Entrican G (2002) Immune regulation during pregnancy and host-pathogen interactions in infectious abortion. J Comp Pathol 126:79–94
Hemphill A, Vonlaufen N, Naguleswaran A (2006) Cellular and immunological basis of the host-parasite relationship during infection with Neospora caninum. Parasitology 133:261–278
López-Gatius F, Almería S, Donofrio G, Nogareda C, Garcia-Ispierto I, Bech-Sabat G, Santolaria P, Yaniz JL, Pabon M, de Sousa NM, Beckers JF (2007) Protection against abortion linked to gamma interferon production in pregnant dairy cows naturally infected with Neospora caninum. Theriogenology 68:1067–1073
Arranz-Solís D, Benavides J, Regidor-Cerrillo J, Horcajo P, Castaño P, del Carmen Ferreras M, Jiménez-Pelayo L, Collantes-Fernández E, Ferre I, Hemphill A (2016) Systemic and local immune responses in sheep after Neospora caninum experimental infection at early, mid and late gestation. Vet Res 47:2
Rettigner C, Lasri S, De Meerschman F, Focant C, Beckers JF, Losson B (2004) Immune response and antigen recognition in non-pregnant ewes experimentally infected with Neospora caninum tachyzoites. Vet Parasitol 122:261–271
Innes EA (2007) The host-parasite relationship in pregnant cattle infected with Neospora caninum. Parasitology 134:1903–1910
Almería S, Serrano-Pérez B, Darwich L, Araujo R, Lopez-Gatius F, Dubey J, Gasbarre L (2014) Maternal and fetal immune response patterns in heifers experimentally infected with Neospora caninum in the second trimester of pregnancy—a descriptive study. Vet Parasitol 204:146–152
Almería S, López-Gatius F (2015) Markers related to the diagnosis and to the risk of abortion in bovine neosporosis. Res Vet Sci 100:169–175
Bartley PM, Wright SE, Maley SW, Macaldowie CN, Nath M, Hamilton CM, Katzer F, Buxton D, Innes EA (2012) Maternal and foetal immune responses of cattle following an experimental challenge with Neospora caninum at day 70 of gestation. Vet Res 43:38
Darwich L, Li Y, Serrano-Pérez B, Mur-Novales R, Garcia-Ispierto I, Cabezón O, López-Gatius F, Almería S (2016) Maternal and foetal cytokine production in dams naturally and experimentally infected with Neospora caninum on gestation day 110. Res Vet Sci 107:55–61
Bartley PM, Kirvar E, Wright S, Swales C, Esteban-Redondo I, Buxton D, Maley SW, Schock A, Rae AG, Hamilton C, Innes EA (2004) Maternal and fetal immune responses of cattle inoculated with Neospora caninum at mid-gestation. J Comp Pathol 130:81–91