期刊论文详细信息
BMC Veterinary Research
Parasite distribution and associated immune response during the acute phase of Toxoplasma gondii infection in sheep
Eric Cox4  Pierre Dorny2  Gary Entrican3  Stéphane De Craeye1  Delfien Verhelst4 
[1] National Reference Laboratory for Toxoplasmosis, Operational Direction Communicable and Infectious Diseases, Scientific Institute of Public Health, Brussels, Belgium;Laboratory of Parasitology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium;Moredun Research Institute, Pentlands Science Park, Bush Loan, Midlothian, Penicuik EH26 0PZ, Scotland, UK;Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
关键词: Sheep;    ELISA;    Quantitative PCR;    Immune responses;    Toxoplasma gondii;   
Others  :  1091718
DOI  :  10.1186/s12917-014-0293-5
 received in 2014-05-27, accepted in 2014-12-02,  发布年份 2014
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【 摘 要 】

Background

In many countries, Toxoplasma gondii (T. gondii) is a major cause of reproductive disorders and abortions in the sheep industry, and therefore responsible for important financial and economic losses. In addition, undercooked infected lamb is an important risk factor for human toxoplasmosis.

In the present study, the initial phase of the infection was investigated: the parasite’s entry site, the subsequent distribution of the parasite and the host-immune response.

Results

Parasite DNA was already detected in the cranial small intestinal mucosa the first days after oral infection with T. gondii tissue cysts. Simultaneously, high IFN-gamma and IL-12 responses were induced mainly in the mesenteric lymph nodes. The emergence of IgG1 (at 8dpi), and IgG2 (at 11 dpi) was accompanied by a decrease or even disappearance of the IFN-gamma and IL-12 response in the Peyers’ patches (PP), PBMC’s and popliteal LN’s. Meanwhile the parasite DNA could be recovered from most mucosal and systemic tissues to become undetectable in the small intestine, popliteal LN, PBMC and spleen 3 weeks pi.

Conclusions

Our results indicate that parasites enter the cranial small intestine the first days after infection and that after an increase the first two weeks after infection, the parasite DNA levels in the intestine drop below the detection limit three weeks after infection. This coincides with an increase in parastic-specific serum IgG1 and IgG2 and a decrease of the antigen-specific IFN-gamma response in PP, PBMC and popliteal LN. We suggest a role for IFN-gamma and IL-12 in controlling the infection.

【 授权许可】

   
2014 Verhelst et al.; licensee BioMed Central.

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【 参考文献 】
  • [1]Cenci-Goga BT, Rossitto PV, Sechi P, McCrindle CM, Cullor JS: Toxoplasma in animals, food, and humans: an old parasite of new concern. Foodborne Pathog Dis 2011, 8:751-762.
  • [2]Buxton D, Maley SW, Wright SE, Rodger S, Bartley P, Innes EA: Toxoplasma gondii and ovine toxoplasmosis: new aspects of an old story. Vet Parasitol 2007, 149:25-28.
  • [3]EFSA, 2007. Scientific opinion of the panel on Biological Hazards and Animal Health Animal Welfare on a request from the European Food Safety Authority (self mandate) to issue a scientific opinion on the review of the Community Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Antimicrobial Resistance in the European Union in 2005.EFSA J 1–32 (http://www.efsa.europa.eu/en/scdocs/doc/600.pdf)
  • [4]VIDA: Veterinary Investigation Surveillance Report. 2009.
  • [5]Cook AJ, Gilbert RE, Buffolano W, Zufferey J, Petersen E, Jenum PA, Foulon W, Semprini AE, Dunn DT: Sources of toxoplasma infection in pregnant women: European multicentre case–control study. European Research Network on Congenital Toxoplasmosis. BMJ 2000, 321:142-147.
  • [6]Dubey JP, Beattie CP: Toxoplasmosis of Animals and Man. CRC Press, Inc, Boca Raton, FL 33431, USA; 1988.
  • [7]Innes EA, Bartley PM, Maley S, Katzer F, Buxton D: Veterinary vaccines against Toxoplasma gondii. Mem Inst Oswaldo Cruz 2009, 104:246-251.
  • [8]Esteban-Redondo I, Innes EA: Toxoplasma gondii infection in sheep and cattle. Comp Immunol Microbiol Infect Dis 1997, 20:191-196.
  • [9]Pappas G, Roussos N, Falagas ME: Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol 2009, 39:1385-1394.
  • [10]Rodger SM, Maley SW, Wright SE, Mackellar A, Wesley F, Sales J, Buxton D: Role of endogenous transplacental transmission in toxoplasmosis in sheep. Vet Rec 2006, 159:768-772.
  • [11]Buxton D: Protozoan infections (Toxoplasma gondii, Neospora caninum and Sarcocystis spp.) in sheep and goats: recent advances. Vet Res 1998, 29:289-310.
  • [12]Morley EK, Williams RH, Hughes JM, Terry RS, Duncanson P, Smith JE, Hide G: Significant familial differences in the frequency of abortion and Toxoplasma gondii infection within a flock of Charollais sheep. Parasitology 2005, 131:181-185.
  • [13]Morley EK, Williams RH, Hughes JM, Thomasson D, Terry RS, Duncanson P, Smith JE, Hide G: Evidence that primary infection of Charollais sheep with Toxoplasma gondii may not prevent foetal infection and abortion in subsequent lambings. Parasitology 2008, 135:169-173.
  • [14]Dubey JP: Toxoplasmosis in sheep–the last 20 years. Vet Parasitol 2009, 163:1-14.
  • [15]Williams RH, Morley EK, Hughes JM, Duncanson P, Terry RS, Smith JE, Hide G: High levels of congenital transmission of Toxoplasma gondii in longitudinal and cross-sectional studies on sheep farms provides evidence of vertical transmission in ovine hosts. Parasitology 2005, 130:301-307.
  • [16]Innes EA, Bartley PM, Buxton D, Katzer F: Ovine toxoplasmosis. Parasitology 2009, 136:1887-1894.
  • [17]Innes EA, Panton WR, Thomson KM, Maley S, Buxton D: Kinetics of interferon gamma production in vivo during infection with the S48 vaccine strain of Toxoplasma gondii. J Comp Pathol 1995, 113:89-94.
  • [18]Innes EA, Vermeulen AN: Vaccination as a control strategy against the coccidial parasites Eimeria, toxoplasma and neospora. Parasitology 2006, 133(Suppl):S145-S168.
  • [19]Blewett DA, Miller JK, Buxton D: Response of immune and susceptible ewes to infection with Toxoplasma gondii. Vet Rec 1982, 111:175-178.
  • [20]Blewett DA, Watson WA: The epidemiology of ovine toxoplasmosis. II. possible sources of infection in outbreaks of clinical disease. Br Vet J 1983, 139:546-555.
  • [21]Buxton D, Maley SW, Wright SE, Rodger S, Bartley P, Innes EA: Ovine toxoplasmosis: transmission, clinical outcome and control. Parassitologia 2007, 49:219-221.
  • [22]Hunter CA, Subauste CS, Remington JS: The role of cytokines in toxoplasmosis. Biotherapy 1994, 7:237-247.
  • [23]Torres-Morales E, Taborda L, Cardona N, De-la-Torre A, Sepulveda-Arias JC, Patarroyo MA, Gomez-Marin JE: Th1 and Th2 immune response to P30 and ROP18 peptides in human toxoplasmosis. Med Microbiol Immunol 2014, 203(5):315-321.
  • [24]Bivas-Benita M, Laloup M, Versteyhe S, Dewit J, De Braekeleer J, Jongert E, Borchard G: Generation of Toxoplasma gondii GRA1 protein and DNA vaccine loaded chitosan particles: preparation, characterization, and preliminary in vivo studies. Int J Pharm 2003, 266:17-27.
  • [25]Martrou P, Pestre M, Loubet R, Nicolas A, Malinvaud G: La toxoplasmose congénitale (note concernant un cas mortel). Limousin Med 1965, 53:3-7.
  • [26]Verhelst D, De Craeye S, Dorny P, Melkebeek V, Goddeeris B, Cox E, Jongert E: IFN-gamma expression and infectivity of Toxoplasma infected tissues are associated with an antibody response against GRA7 in experimentally infected pigs. Vet Parasitol 2011, 179:14-21.
  • [27]Aubert D, Maine GT, Villena I, Hunt JC, Howard L, Sheu M, Brojanac S, Chovan LE, Nowlan SF, Pinon JM: Recombinant antigens to detect Toxoplasma gondii-specific immunoglobulin G and immunoglobulin M in human sera by enzyme immunoassay. J Clin Microbiol 2000, 38:1144-1150.
  • [28]Bonhomme A, Maine GT, Beorchia A, Burlet H, Aubert D, Villena I, Hunt J, Chovan L, Howard L, Brojanac S, Sheu M, Tyner J, Pluot M, Pinon JM: Quantitative immunolocalization of a P29 protein (GRA7), a new antigen of toxoplasma gondii. J Histochem Cytochem 1998, 46:1411-1422.
  • [29]Jacobs D, Vercammen M, Saman E: Evaluation of recombinant dense granule antigen 7 (GRA7) of Toxoplasma gondii for detection of immunoglobulin G antibodies and analysis of a major antigenic domain. Clin Diagn Lab Immunol 1999, 6:24-29.
  • [30]Holec-Gasior L: Toxoplasma gondii recombinant antigens as tools for serodiagnosis of human toxoplasmosis: current status of studies. Clin Vaccine Immunol 2013, 20:1343-1351.
  • [31]Fischer HG, Stachelhaus S, Sahm M, Meyer HE, Reichmann G: GRA7, an excretory 29 kDa Toxoplasma gondii dense granule antigen released by infected host cells. Mol Biochem Parasitol 1998, 91:251-262.
  • [32]Jongert E, Verhelst D, Abady M, Petersen E, Gargano N: Protective Th1 immune responses against chronic toxoplasmosis induced by a protein-protein vaccine combination but not by its DNA-protein counterpart. Vaccine 2008, 26:5289-5295.
  • [33]Vercammen M, Scorza T, Huygen K, De Braekeleer J, Diet R, Jacobs D, Saman E, Verschueren H: DNA vaccination with genes encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2 induces partially protective immunity against lethal challenge in mice. Infect Immun 2000, 68:38-45.
  • [34]Vandenbroeck K, Nauwynck H, Vanderpooten A, Van Reeth K, Goddeeris B, Billiau A: Recombinant porcine IFN-gamma potentiates the secondary IgG and IgA responses to an inactivated suid herpesvirus-1 vaccine and reduces postchallenge weight loss and fever in pigs. J Interferon Cytokine Res 1998, 18:739-744.
  • [35]Vande Walle K, De Zutter L, Cox E: Oral infection with a Shiga toxin-negative Escherichia coli O157:H7 strain elicits humoral and cellular responses but does not protect sheep from colonisation with the homologous strain. Vet Microbiol 2011, 148:317-322.
  • [36]James GT: Inactivation of the protease inhibitor phenylmethylsulfonyl fluoride in buffers. Anal Biochem 1978, 86:574-579.
  • [37]Kijlstra A, Meerburg B, Cornelissen J, De Craeye S, Vereijken P, Jongert E: The role of rodents and shrews in the transmission of Toxoplasma gondii to pigs. Vet Parasitol 2008, 156:183-190.
  • [38]Cardoso LS, Araujo MI, Goes AM, Pacifico LG, Oliveira RR, Oliveira SC: Polymyxin B as inhibitor of LPS contamination of Schistosoma mansoni recombinant proteins in human cytokine analysis. Microb Cell Fact 2007, 6:1. BioMed Central Full Text
  • [39]Hope JC, Kwong LS, Thom M, Sopp P, Mwangi W, Brown WC, Palmer GH, Wattegedera S, Entrican G, Howard CJ: Development of detection methods for ruminant interleukin (IL)-4. J Immunol Methods 2005, 301:114-123.
  • [40]Sibley LD, Khan A, Ajioka JW, Rosenthal BM: Genetic diversity of Toxoplasma gondii in animals and humans. Philos Trans R Soc Lond B Biol Sci 2009, 364:2749-2761.
  • [41]Tenter AM, Heckeroth AR, Weiss LM: Toxoplasma gondii: from animals to humans. Int J Parasitol 2000, 30:1217-1258.
  • [42]Benavides J, Maley S, Pang Y, Palarea J, Eaton S, Katzer F, Innes EA, Buxton D, Chianini F: Development of lesions and tissue distribution of parasite in lambs orally infected with sporulated oocysts of Toxoplasma gondii. Vet Parasitol 2011, 179:209-215.
  • [43]Dubey JP: History of the discovery of the life cycle of Toxoplasma gondii. Int J Parasitol 2009, 39:877-882.
  • [44]Falcon J, Freyre A: Toxoplasma gondii: prototype immunization of lambs against formation of muscle and brain cysts. Vet Parasitol 2009, 166:15-20.
  • [45]Gutierrez J, O’Donovan J, Williams E, Proctor A, Brady C, Marques PX, Worrall S, Nally JE, McElroy M, Bassett H, Sammin D, Buxton D, Maley S, Markey BK: Detection and quantification of Toxoplasma gondii in ovine maternal and foetal tissues from experimentally infected pregnant ewes using real-time PCR. Vet Parasitol 2010, 172:8-15.
  • [46]Race R, Jenny A, Sutton D: Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. J Infect Dis 1998, 178:949-953.
  • [47]Abu-Dalbouh MA, Ababneh MM, Giadinis ND, Lafi SQ: Ovine and caprine toxoplasmosis (Toxoplasma gondii) in aborted animals in Jordanian goat and sheep flocks. Trop Anim Health Prod 2012, 44:49-54.
  • [48]Dubey JP: Toxoplasma gondii cysts in placentas of experimentally infected sheep. Am J Vet Res 1987, 48:352-353.
  • [49]Riyadh R: Flock Level Sero-Prevalence of and Risk Factors for Toxoplasma Gondii in Sheep and Goats in Northern Jordan. Jordan University of Science and Technology, Irbid, Jordan; 2005.
  • [50]Coughlan SN, Saman E, Jacobs D, Mercier C, Cesbron-Delauw MF, Trees AJ: Cellular and humoral immune responses to recombinant antigens in sheep infected with Toxoplasma gondii. Parasite Immunol 1995, 17:465-468.
  • [51]Buxton D, Thomson KM, Maley S, Wastling JM, Innes EA, Panton WR, Nicoll S: Primary and secondary responses of the ovine lymph node to Toxoplasma gondii: cell output in efferent lymph and parasite detection. J Comp Pathol 1994, 111:231-241.
  • [52]Innes EA, Panton WR, Sanderson A, Thomson KM, Wastling JM, Maley S, Buxton D: Induction of CD4+ and CD8+ T cell responses in efferent lymph responding to Toxoplasma gondii infection: analysis of phenotype and function. Parasite Immunol 1995, 17:151-160.
  • [53]Wastling JM, Nicoll S, Buxton D: Comparison of two gene amplification methods for the detection of Toxoplasma gondii in experimentally infected sheep. J Med Microbiol 1993, 38:360-365.
  • [54]McColgan C, Buxton D, Miller HR: Studies on ovine efferent lymph following infection with Toxoplasma gondii. J Comp Pathol 1987, 97:695-703.
  • [55]Dubey JP, Sharma SP: Parasitemia and tissue infection in sheep fed Toxoplasma gondii oocysts. J Parasitol 1980, 66:111-114.
  • [56]Sher A, Oswald IP, Hieny S, Gazzinelli RT: Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-alpha. J Immunol 1993, 150:3982-3989.
  • [57]Gazzinelli RT, Hakim FT, Hieny S, Shearer GM, Sher A: Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. J Immunol 1991, 146:286-292.
  • [58]Gazzinelli RT, Denkers EY, Sher A: Host resistance to Toxoplasma gondii: model for studying the selective induction of cell-mediated immunity by intracellular parasites. Infect Agents Dis 1993, 2:139-149.
  • [59]Bhopale GM: Development of a vaccine for toxoplasmosis: current status. Microbes Infect 2003, 5:457-462.
  • [60]Gazzinelli RT, Wysocka M, Hayashi S, Denkers EY, Hieny S, Caspar P, Trinchieri G, Sher A: Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol 1994, 153:2533-2543.
  • [61]Vossenkamper A, Struck D, Alvarado-Esquivel C, Went T, Takeda K, Akira S, Pfeffer K, Alber G, Lochner M, Forster I, Liesenfeld O: Both IL-12 and IL-18 contribute to small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii, but IL-12 is dominant over IL-18 in parasite control. Eur J Immunol 2004, 34:3197-3207.
  • [62]Denkers EY, Gazzinelli RT: Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin Microbiol Rev 1998, 11:569-588.
  • [63]Morampudi V, De Craeye S, Le Moine A, Detienne S, Braun MY, D’Souza S: Partial depletion of CD4(+)CD25(+)Foxp3(+) T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice. Microbes Infect 2011, 13:394-404.
  • [64]Tenter AM, Vietmeyer C, Johnson AM: Development of ELISAs based on recombinant antigens for the detection of Toxoplasma gondii-specific antibodies in sheep and cats. Vet Parasitol 1992, 43:189-201.
  • [65]Verma SP, Bhardwaj RM, Gautam OP: Application of countercurrent immunoelectrophoresis (CIEP) in the sero-diagnosis of Toxoplasma antibodies in sheep. J Vet Parasitol 1989, 3:61-62.
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