Relationship Between IFN${\gamma}$ Production, Antibody and Hormone Levels in Naturally Neospora caninum-infected Pregnant Dairy Cows

Neospora caninum에 자연 감염된 임신우에서 IFN${\gamma}$, 항체 및 호르몬 수준의 상관관계

  • Son, Jeong-Hoon (College of Veterinary Medicine, Research Institute of Veterinary Science, Chungnam National University) ;
  • Park, Bae-Keun (College of Veterinary Medicine, Research Institute of Veterinary Science, Chungnam National University) ;
  • Son, Hwa-Young (College of Veterinary Medicine, Research Institute of Veterinary Science, Chungnam National University) ;
  • Jung, Ju-Young (College of Veterinary Medicine, Research Institute of Veterinary Science, Chungnam National University) ;
  • Park, Sang-Joon (College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Tae-Hwan (College of Veterinary Medicine, Kyungpook National University) ;
  • Cho, Sung-Whan (College of Veterinary Medicine, Research Institute of Veterinary Science, Chungnam National University) ;
  • Ryu, Si-Yun (College of Veterinary Medicine, Research Institute of Veterinary Science, Chungnam National University)
  • 손정훈 (충남대학교 수의과대학 및 동물의과학연구소) ;
  • 박배근 (충남대학교 수의과대학 및 동물의과학연구소) ;
  • 손화영 (충남대학교 수의과대학 및 동물의과학연구소) ;
  • 정주영 (충남대학교 수의과대학 및 동물의과학연구소) ;
  • 박상준 (경북대학교 수의과대학) ;
  • 김태환 (경북대학교 수의과대학) ;
  • 조성환 (충남대학교 수의과대학 및 동물의과학연구소) ;
  • 류시윤 (충남대학교 수의과대학 및 동물의과학연구소)
  • Accepted : 2010.09.17
  • Published : 2010.12.31

Abstract

Neosporosis is a widespread parasitic disease caused by Neospora caninum, an intracellular protozoan parasite. It causes economic losses due to reproductive failure. The potential relationship between pregnancy outcomes and levels of IFN${\gamma}$, hormones, and antibodies in naturally N. caninum-infected cows was examined in the blood samples collected every 2 or 4 weeks in 26 pregnant cows from 4 different farms. The mean S/P value of seropositive nonaborting animals (n = 14) reached peak levels 15 weeks prior to parturition, and declined thereafter to parturition. The S/P value 13 weeks prior to abortion in seropositive aborting cows (n=3) remained at high levels, and abortions occurred at 20 (142 days), 26 (185 days), and 28 weeks (199 days) after artificial insemination. IFN${\gamma}$ levels in the seropositive non-aborting group varied by individuals and gestational periods; IFN${\gamma}$ levels stayed at elevated levels or increased abruptly close to abortion in seropositive aborting cows. IFN${\gamma}$ level patterns in the seronegative group (n = 9) were similar to the seropositive non-aborting group, although IFN${\gamma}$ amounts were lower than the seropositive group. The mean progesterone levels in the seropositive non-aborting and seronegative groups decreased markedly 7 weeks prior to parturition. The mean progesterone levels 5 and 7 weeks prior to abortion were lower than the other groups 5 and 7 weeks prior to parturition. The mean 17${\beta}$-estradiol levels in the seropositive aborting cows increased close to abortion; the produced amounts were lower than those of seropositive non-aborting and seronegative groups close to parturition. These results suggested that lower levels of progesterone and ${\beta}$-estradiol in Neospora-infected cows may lead to increases in IFN${\gamma}$ production and in turn may result in abortion.

네오스포라 감염증은 세포내성 원충성 기생충인 Neospora caninum에 의해 발생하는 질병으로 전세계적으로 발생하고 있으며, 소에서는 번식장해로 인한 막대한 경제적 손실을 유발한다. 본 연구는 4 곳의 각기 다른 목장으로부터 N. caninum에 자연 감염된 양성우와 음성우를 포함한 26두의 임신우를 선정하여 2주 내지 4주 간격으로 혈액을 채취하여 호르몬, 항체가, IFN${\gamma}$ 수준과 유산 혹은 분만과의 상관관계를 조사하였다. 유산하지 않은 Neospora 양성우14두의 S/P 평균값은 분만 전 15주에 최고치를 보였고, 이후 분만 때까지 감소하였다. 유산한 양성우 3두의 유산 시기는 각각 인공 수정 후 20주 (142일), 26주 (185일), 28주 (199일)였으며, 이들의 S/P값은 유산 전 13주부터 유산 때까지 높은 수준을 유지하였다. 유산하지 않은 양성우에서 IFN${\gamma}$ 수준은 개체에 따라 그리고 동일한 개체라도 임신기간이 경과함에 따라 다양하게 나타났으며, 유산한 양성우에서 IFN${\gamma}$ 수준은 계속 높은 상태를 유지하거나 또는 유산시점에 근접하여 급상승하였다. Neospora 음성우 9두의 IFN${\gamma}$ 수준은 양성우보다 낮았지만, 그 양상은 유산하지 않은 양성우와 유사하였다. 유산하지 않은 양성우와 음성우에서 평균적인 progesterone수준은 분만 전 7주부터 뚜렷하게 감소하였다. 유산한 양성우에서는 유산 전 5주와 7주의 평균적인 progesterone 수준은 정상 분만한 음성우나 양성우의 분만전 5주와 7주에 측정된 평균 progesterone 수준보다 낮았다. 유산한 양성우에서 17${\beta}$-estradiol의 평균 수준은 유산 시점에 근접할수록 증가하였지만, 혈청내 총양은 유산하지 않은 양성우와 음성우에서 분만시점에 근접하여 측정한 평균 17${\beta}$-estradiol 수준보다 더 낮았다. 이상의 결과로 미루어 보아 Neospora에 감염된 소에서 17${\beta}$-estradiol과 progesterone 수준의 저하는 IFN${\gamma}$ 산생을 증가시켜, 결국에는 유산을 초래할 수 있다고 생각된다.

Keywords

References

  1. Aksoy S, Celikkanat H, Senoz S, Gokmen O: The prognostic value of serum estradiol, progesterone, testosterone and free testosterone levels in detecting early abortions. Eur J Obstet Gynecol Reprod Biol 1996; 67: 5-8. https://doi.org/10.1016/0301-2115(96)02421-9
  2. Almeria S, Nogareda C, Santolaria P, Garcia-Ispierto I, Yaniz JL, Lopez-Gatius F. Specific anti-Neospora caninum IgG1 and IgG2 antibody responses during gestation in naturally infected cattle and their relationship with gamma interferon production. Vet Immunol Immunolpathol 2009; 130: 35-42. https://doi.org/10.1016/j.vetimm.2009.01.003
  3. Anderson ML, Andrianarivo AG, Conrad PA. Neosporosis in cattle. Anim Reprod Sci 2000; 60-61: 417-431. https://doi.org/10.1016/S0378-4320(00)00117-2
  4. Arck P, Hansen PJ, Jericvic BM, Piccinni MP, Szekeres-Bartho J. Progesterone during pregnancy: endocrine-immune cross talk in mammalian species and the role of stress. Am J Reprod Immunol 2007; 58: 268-279. https://doi.org/10.1111/j.1600-0897.2007.00512.x
  5. Bech-Sabat G, Lopez-Gatius F, Santolaria P, Garcia-Ispierto I, Pabon M, Nogareda C, Yaniz JL, Almeria S. Progesterone supplementation during mid-gestation increases the risk of abortion in Neospora-infected dairy cows with high antibody titers. Vet Parasitol 2007; 145: 164-167. https://doi.org/10.1016/j.vetpar.2006.11.018
  6. Dannatt L. Neospora caninum antibody levels in an endemically infected dairy herd. J Br Cattle Vet Assoc 1997; 5: 335-337.
  7. Druckmann R, Druckmann MA. Progesterone and the immunology of pregnancy. J Steroid Biochem Mol Biol 2005; 97: 389-396. https://doi.org/10.1016/j.jsbmb.2005.08.010
  8. Dubey JP, Buxton D, Wouda W. Pathogenesis of bovine neosporosis. J Comp Path 2006; 134: 267-289. https://doi.org/10.1016/j.jcpa.2005.11.004
  9. Dubey JP, Lindsay DS. A review of Neospora caninum and neosporosis. Vet Parasitol 1996; 67: 1-59. https://doi.org/10.1016/S0304-4017(96)01035-7
  10. Dubey JP, Schares G. Diagnosis of bovine neosporosis. Vet Parasitol 2006; 140: 1-34. https://doi.org/10.1016/j.vetpar.2006.03.035
  11. Dubey JP, Schares G, Ortega-Mora LM. Epidemiology and control neosporosis and Neospora caninum. Clin Microbio Rev 2007; 20: 323-367 https://doi.org/10.1128/CMR.00031-06
  12. Entrican G. Immune regulation during pregnancy and host-pathogen interactions in infectious abortion. J Comp Path 2002; 26: 79-94.
  13. Garcia-ispierto I, Nogareda C, Yaniz JL, Almeria S, Martinez-Bello D, de Sousa NM, Becker JF, Lopez-Gatius F. Neospora caninum and Coxiella burnetii seropositivity are related to endocrine pattern changes during gestation in lactating dairy cows. Theriogenology 2010; 74: 212-220. https://doi.org/10.1016/j.theriogenology.2010.02.004
  14. Innes EA, Andrianarivo AG, Björkman C, Williams DJL, Conrad PA. Immune responses to Neospora caninum and prospects for vaccination. Trends Parasitol 2002; 18: 187-195.
  15. Innes EA, Wright S, Bartley P, Maley S, Macaldowie C, Esteban-Redondo I, Buxton D. The host-parasite relationship in bovine neosporosis. Vet Immunol Immunopathol 2005; 108: 29-36. https://doi.org/10.1016/j.vetimm.2005.07.004
  16. Jenkins MC. Advances and prospects for subunit vaccines against protozoa of veterinary importance. Vet Parasitol 2001; 101: 291-310. https://doi.org/10.1016/S0304-4017(01)00557-X
  17. Kano R, Kudo A, Kamiya H, Kobayashi Y, Maeda R, Omata Y. C57BL/6 mice infected with Neospora caninum during administration of progesterone show bias toward type 2 immune response. J Vet Med Sci 2007; 69: 1095-1097. https://doi.org/10.1292/jvms.69.1095
  18. Kobayashi A, Katagiri S, Kimura T, Ochiai K, Umemura T. Steroid hormones do not reactivate Neospora caninum in ovariectomized mice. J Vet Med Sci 2002; 64: 773-777. https://doi.org/10.1292/jvms.64.773
  19. Lopez-Gatius F, Almeria S, Donofrio G, Nogareda C, Garciaispierto I, Bech-Sabat G, Santolaria P, Yaniz JL, Pabon M, de Sousa NM, Beckers JF. Protection against abortion linked to gamma interferon production in pregnant dairy cows naturally infected with Neospora caninum. Theriogenology 2007; 68: 1067-1073. https://doi.org/10.1016/j.theriogenology.2007.08.006
  20. Lopez-Gatius F, Lopez-Bejar M, Murugavel K, Pabon M, Ferrer D, Almeria S. Neospora-associated abortion episode over a 1-year period in a dairy herd in north-east spain. J Vet Med B 2004; 51: 348-352.
  21. Maley SW, Buxton D, Macaldowie CN, Anderson IE, Wright SE, Bartley PM, Esteban-Redondo I, Hamilton CM, Storset AK, Innes EA. Characterization of the immune response in the placenta of cattle experimentally infected with Neospora caninum in early gestation. J Comp Path 2006; 135: 130-141. https://doi.org/10.1016/j.jcpa.2006.07.001
  22. Matejuk A, Adlard K, Zamora A, Silverman M, Vandenbark AA, Offner H. 17$\beta$-estradiol inhibits cytokine, chemokine, and chemokine receptor mRNA expression in the central nervous system of female mice with experimental autoimmune encephalomyelitis. J Neurosci Res 2001; 65: 529-542. https://doi.org/10.1002/jnr.1183
  23. Nogareda C, Lopez-Gatius F, Santolaria P, Garcia_ispierto I, Bech-Sabat G, Pabon M, Meso M, Gonzalez-Warleta M, Castro-Hermida JA, Yaniz JL, Almeria S. Dynamics of anti-Neospora caninum antibodies during gestation in chronically infected dairy cows. Vet Parasitol 2007; 148: 193-199. https://doi.org/10.1016/j.vetpar.2007.06.032
  24. Pabon M, Lopez-Gatius F, Garcia-Ispierto I, Bech-Sabat G, Nogareda C, Almeria S. Chronic Neospora caninum infection and repeat abortion in dairy cows: a 3-year study. Vet Parasitol 2007; 147: 40-46. https://doi.org/10.1016/j.vetpar.2007.03.017
  25. Pape-Zambito DA, Magliaro AL, Kensinger RS. 17$\beta$-estradiol and estrogen concentrations in plasma and milk during bovine pregnancy. J Dairy Sci 2008; 91: 127-135. https://doi.org/10.3168/jds.2007-0481
  26. Park BK, Kim HS, Ryu SY, Cho SW, Kang SW. A case report of bovine abortion induced by Neospora sp. in Korea. J Vet Sci CNU 1998; 6: 43-47
  27. Patel OV, Takenouchi N, Takahashi T, Hirako M, Sasaki N. Plasma oestrone and oestradiol concentrations throughout gestation in cattle: relationship to stage of gestation and fetal number. Res Vet Sci 1999; 66: 129-133. https://doi.org/10.1053/rvsc.1998.0254
  28. Piccinni MP, Giudizi MG, Biagiotti R, Beloni L, Giannarini L, Sampognaro S, Parronchi P, Manetti R, Annunziato F, Livi C, Romagnani S, Maggi E. Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J Immunol 1995; 155: 128-133.
  29. Piccinni MP, Scaletti C, Maggi E, Romagnani S. Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J Neuroimmunol 2000; 109: 30-33. https://doi.org/10.1016/S0165-5728(00)00299-X
  30. Pope GS, Gupta SK, Munro IB. Progesterone levels in the systemic plasma of pregnant, cycling and ovariectomized cows. J Reprod Fert 1969; 20: 369-381 https://doi.org/10.1530/jrf.0.0200369
  31. Quinn HE, Ellis JT, Smith NC. Neospora caninum: a cause of immunemediated failure of pregnancy? Trends Parasitol 2002; 18: 391-394. https://doi.org/10.1016/S1471-4922(02)02324-3
  32. Salem ML. Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy 2004; 3: 97-104. https://doi.org/10.2174/1568010043483944
  33. Salem ML, Matsuzaki G, Madkour GA, Nomoto K. Beta-estradiol-induced decrease in IL-12 and TNF-$\alpha$ expression suppresses macrophage functions in the course of Listeria monocytogenes infection in mice. Int J Immunopharmacol 1999; 21: 481-497. https://doi.org/10.1016/S0192-0561(99)00027-2
  34. Sauer MV, Sinosich MJ, Yeko TR, Vermesh M, Buster JE, Simon JA. Predictive value of a single serum pregnancy associated plasma protein-A or progesterone in the diagnosis of abnormal pregnancy. Human Reprod 1989; 4: 331-334.
  35. Stenlund S, Kindahl H, Magnusson U, Uggla A, Bjorkman C. Serum antibody profile and reproductive performance during two consecutive pregnancies of cows naturally infected with Neospora caninum. Vet Parasitol 1999; 85: 227-234. https://doi.org/10.1016/S0304-4017(99)00120-X
  36. Takeuchi T, Nishii O, Okamura T, Yaginuma T, Kawana T. Free testosterone and abortion in early pregnancy. Int J Gynaecol Obstet 1993; 43: 151-156. https://doi.org/10.1016/0020-7292(93)90322-N
  37. Trees AJ, Davison HC, Innes EA, Wastling JM. Towards evaluating the economic impact of bovine neosporosis. Int J Parasitol 1999; 29: 1195-1200. https://doi.org/10.1016/S0020-7519(99)00093-4
  38. Williams DJL, Guy CS, McGarry JW, Guy F, Tasker L, Smith RF, MacEachern K, Cripps PJ, Kelly DF, Trees AJ. Neospora caninum-associated abortion in catle: the time of experimentally-induced parasitaemia during gestation determines foetal survival. Parasitology 2000; 121: 347-358. https://doi.org/10.1017/S0031182099006587
  39. Williams DJL, Guy CS, Smith RF, Guy F, McGarry JW, McKay JS, Trees AJ. First demonstration of protective immunity against foetopathy in cattle with latent Neospora caninum infection. Int J parasitol 2003; 33: 1059-1065. https://doi.org/10.1016/S0020-7519(03)00143-7