A Comprehensive Review of Toxoplasma Gondii Biology and Host-Cell Interaction: Challenges for a Plant-Based Vaccine

  • Valeria Sander
  • Sergio O. Angel
  • Marina ClementeEmail author


Toxoplasmosis is a worldwide-distributed infection caused by Toxoplasma gondii, which causes a wide range of clinical syndromes in humans, mammals and birds. T. gondii is considered a parasite of veterinary and medical importance, because it may cause abortion or congenital disease in its intermediate hosts. Despite the economic losses associated with T. gondii infection in farm animals and the socio-economic impact caused by this zoonotic disease in the human population, there is no effective treatment available for humans or animals able to eliminate the parasite from the host once the chronic infection has been established. The only commercial vaccine is the S48 strain of attenuated tachyzoites for use in sheep. However, this vaccine causes side effects, has a short life time and induces a short-term immunity. So far, no acellular vaccine against toxoplasmosis has been commercialized. In fact, future challenges include the development of an effective vaccine to prevent toxoplasmosis. Most parasitologists and vaccinologists agree that future efforts should be concentrated on developing multi-antigen vaccines and more efficient delivery systems able to express heterologous proteins abundantly as well as on searching for immunization schedules and adequate adjuvants to enhance the protective responses. To achieve this, platforms for the production of acellular vaccines based on the use of plants can have an important role.


Plant vaccine Toxoplasmosis Immune response SAG1 GRA4 


  1. Ahmad P, Ashraf M, Younis M et al (2012) Role of transgenic plants in agriculture and biopharming. Biotechnol Adv 30(3):524–540. Scholar
  2. Albarracín RM, Becher ML, Farran I et al (2015) The fusion of Toxoplasma gondii SAG1 vaccine candidate to Leishmania infantum heat shock protein 83-kDa improves expression levels in tobacco chloroplasts. Biotechnol J 10(5):748–759. Scholar
  3. Altcheh J, Diaz NS, Pepe CM et al (2006) Kinetic analysis of the humoral immune response against 3 Toxoplasma gondii-recombinant proteins in infants with suspected congenital toxoplasmosis. Diagn Microbiol Infect Dis 56(2):161–165CrossRefPubMedGoogle Scholar
  4. Alves CM, Silva DA, Azzolini AE et al (2013) Galectin-3 is essential for reactive oxygen species production by peritoneal neutrophils from mice infected with a virulent strain of Toxoplasma gondii. Parasitology 140(2):210–219. Scholar
  5. Ayaz E, Türkoğlu ŞA, Orallar H (2016) Toxoplasma gondii and Epilepsy. Turkiye Parazitol Derg 40(2):90–96. Scholar
  6. Azevedo KM, Setúbal S, Lopes VG et al (2010) Congenital toxoplasmosis transmitted by human immunodeficiency-virus infected women. Braz J Infect Dis 14(2):186–189CrossRefPubMedGoogle Scholar
  7. Basavaraju A (2016) Toxoplasmosis in HIV infection: an overview. Trop Parasitol 6(2):129–135CrossRefPubMedPubMedCentralGoogle Scholar
  8. Barragan A, Sibley LD (2002) Transepithelial migration of Toxoplasma gondii is linked to parasite motility and virulence. J Exp Med 195(12):1625–1633CrossRefPubMedPubMedCentralGoogle Scholar
  9. Belluco S, Mancin M, Conficoni D et al (2016) Investigating the determinants of Toxoplasma gondii prevalence in meat: a systematic review and meta-regression. PLoS ONE 11(4):e0153856. Scholar
  10. Bereswill S, Kühl AA, Alutis M et al (2014) The impact of Toll-like-receptor-9 on intestinal microbiota composition and extra-intestinal sequelae in experimental Toxoplasma gondii induced ileitis. Gut Pathog 6:19. Scholar
  11. Berinstein A, Vazquez-Rovere C, Asurmendi S et al (2005) Mucosal and systemic immunization elicited by Newcastle disease virus (NDV) transgenic plants as antigens. Vaccine 23(48–49):5583–5589CrossRefPubMedGoogle Scholar
  12. Bertranpetit E, Jombart T, Paradis E et al (2017) Phylogeography of Toxoplasma gondii points to a South American origin. Infect Genet Evol 48:150–155. Scholar
  13. Bierly AL, Shufesky WJ, Sukhumavasi W et al (2008) Dendritic cells expressing plasmacytoid marker PDCA-1 are Trojan horses during Toxoplasma gondii infection. J Immunol 181(12):8485–8491CrossRefPubMedPubMedCentralGoogle Scholar
  14. Blader IJ, Coleman BI, Chen CT et al (2015) Lytic cycle of Toxoplasma gondii: 15 years later. Annu Rev Microbiol 69:463–485. Scholar
  15. Bliss SK, Gavrilescu LC, Alcaraz A et al (2001) Neutrophil depletion during Toxoplasma gondii infection leads to impaired immunity and lethal systemic pathology. Infect Immun 69(8):4898–4905CrossRefPubMedPubMedCentralGoogle Scholar
  16. Bourguin I, Chardès T, Bout D (1993) Oral immunization with Toxoplasma gondii antigens in association with cholera toxin induces enhanced protective and cell-mediated immunity in C57BL/6 mice. Infect Immun 61(5):2082–2088Google Scholar
  17. Bowie WR, King AS, Werker DH et al (1997) Outbreak of toxoplasmosis associated with municipal drinking water. The BC Toxoplasma Investigation Team. Lancet 350(9072):173–177CrossRefPubMedGoogle Scholar
  18. Bresciani KDS, Costa AJ, Toniollo GH et al (1999) Experimental toxoplasmosis in pregnant bitches. Vet Parasitol 86:143–145CrossRefPubMedGoogle Scholar
  19. Bresciani KDS, Toniollo GH, Costa AJ et al (2001) Clinical, parasitological and obstetric observations in pregnant bitches with experimental toxoplasmosis. Ciênc Rur 31:1039–1043CrossRefGoogle Scholar
  20. Bresciani KD, Costa AJ, Toniollo GH et al (2009) Transplacental transmission of Toxoplasma gondii in reinfected pregnant female canines. Parasitol Res 104(5):1213–1217. Scholar
  21. Burg JL, Perelman D, Kasper LH et al (1988) Molecular analysis of the gene encoding the major surface antigen of Toxoplasma gondii. J Immunol 141(10):3584–3591PubMedGoogle Scholar
  22. Buriani G, Mancini C, Benvenuto E et al (2011) Plant heat shock protein 70 as carrier for immunization against a plant-expressed reporter antigen. Transgenic Res 20(2):331–344. Scholar
  23. Buriani G, Mancini C, Benvenuto E et al (2012) Heat-shock protein 70 from plant biofactories of recombinant antigens activate multiepitope-targeted immune responses. Plant Biotechnol J 10(3):363–371. Scholar
  24. Butcher BA, Kim L, Johnson PF et al (2001) Toxoplasma gondii tachyzoites inhibit proinflammatory cytokine induction in infected macrophages by preventing nuclear translocation of the transcription factor NF-kappa B. J Immunol 167(4):2193–2201CrossRefPubMedGoogle Scholar
  25. Buxton D, Thomson K, Maley S (1991) Vaccination of sheep with a live incomplete strain (S48) of Toxoplasma gondii and their immunity to challenge when pregnant. Vet Rec 129(5):89–93CrossRefPubMedGoogle Scholar
  26. Buxton D, Maley SW, Wright SE et al (2007) Toxoplasma gondii and ovine toxoplasmosis: new aspects of an old story. Vet Parasitol 149(1–2):25–28CrossRefPubMedGoogle Scholar
  27. Cañedo-Solares I, Calzada-Ruiz M, Ortiz-Alegría LB et al (2013) Endothelial cell invasion by Toxoplasma gondii: differences between cell types and parasite strains. Parasitol Res 112(8):3029–3033. Scholar
  28. Cardona N, de-la-Torre A, Siachoque H (2009) Toxoplasma gondii: P30 peptides recognition pattern in human toxoplasmosis. Exp Parasitol 123(2):199–202. Scholar
  29. Chebolu S, Daniell H (2007) Stable expression of Gal/GalNAc lectin of Entamoeba histolytica in transgenic chloroplasts and immunogenicity in mice towards vaccine development for amoebiasis. Plant Biotechnol J 5(2):230–239CrossRefPubMedPubMedCentralGoogle Scholar
  30. Chen R, Lu SH, Tong QB, Lou D, Shi DY, Jia BB, Huang GP, Wang JF (2009) Protective effect of DNA-mediated immunization with liposome-encapsulated GRA4 against infection of Toxoplasma gondii. J Zhejiang Univ Sci B 10(7):512–521CrossRefPubMedPubMedCentralGoogle Scholar
  31. Clemente M, Curilovic R, Sassone A et al (2005) Production of the main surface antigen of Toxoplasma gondii in tobacco leaves and analysis of its antigenicity and immunogenicity. Mol Biotechnol 30:41–50CrossRefPubMedGoogle Scholar
  32. Clemente M (2014) Overview of plant-made vaccine antigens against toxoplasmosis. In: Rosales-Mendoza S (ed) Genetically engineered plants as a source of vaccines against wide spread diseases. Springer, New York, pp 215–241. Scholar
  33. Clemente M, Corigliano MG (2012) Overview of plant-made vaccine antigens against malaria. J Biomed Biotechnol 2012:206918. Scholar
  34. Cohen SB, Denkers EY (2014) Border maneuvers: deployment of mucosal immune defenses against Toxoplasma gondii. Mucosal Immunol 7(4):744–752. Scholar
  35. Cook AJC, Gilbert RE, Buffolano W et al (2000) Sources of toxoplasma infection in pregnant women: European multicentre case-control study. BMJ 321:142–147CrossRefPubMedPubMedCentralGoogle Scholar
  36. Corigliano MG, Maglioco A, Becher ML, Goldman A, Martín V, Angel SO, Clemente M, Kanellopoulos J (2011) Plant Hsp90 proteins interact with B-Cells and stimulate their proliferation. PLoS ONE 6(6):e21231CrossRefPubMedPubMedCentralGoogle Scholar
  37. Corigliano MG, Fenoy I, Sander V et al (2013) Plant heat shock protein 90 as carrier-adjuvant for immunization against a reporter antigen. Vaccine 31(49):5872–5878. Scholar
  38. Coster LO (2013) Parasitic infections in solid organ transplant recipients. Infect Dis Clin North Am 27(2):395–427. Scholar
  39. Dabritz HA, Miller MA, Atwill ER et al (2007) Detection of Toxoplasma gondii-like oocysts in cat feces and estimates of the environmental oocyst burden. J Am Vet Med Assoc 231(11):1676–1684CrossRefPubMedGoogle Scholar
  40. Debierre-Grockiego F, Campos MA, Azzouz N et al (2007) Activation of TLR2 and TLR4 by glycosylphosphatidylinositols derived from Toxoplasma gondii. J Immunol 179(2):1129–1137CrossRefPubMedGoogle Scholar
  41. Del Grande C, Galli L, Schiavi E (2017) Is Toxoplasma gondii a trigger of bipolar disorder? Pathogens 10;6(1): pii E3.
  42. Del Rio L, Bennouna S, Salinas J et al (2001) CXCR2 deficiency confers impaired neutrophil recruitment and increased susceptibility during Toxoplasma gondii infection. J Immunol 167(11):6503–6509CrossRefPubMedGoogle Scholar
  43. Del Yácono LM, Farran I, Becher ML et al (2012) Chloroplast-derived Toxoplasma gondii GRA4 antigen used as an oral vaccine protects against toxoplasmosis in mice. Plant Biotechnol J 10(9):1136–1144. Scholar
  44. Delhaes L, Ajzenberg D, Sicot B et al (2010) Severe congenital toxoplasmosis due to a Toxoplasma gondii strain with an atypical genotype: case report and review. Prenat Diagn 30(9):902–905. Scholar
  45. Denkers EY, Scharton-Kersten T, Barbieri S et al (1996) A role for CD4+ NK1.1+ T lymphocytes as major histocompatibility complex class II independent helper cells in the generation of CD8+ effector function against intracellular infection. J Exp Med 184(1):131–139CrossRefPubMedGoogle Scholar
  46. Denkers EY, Schneider AG, Cohen SB, Butcher BA (2012) Phagocyte responses to protozoan infection and how Toxoplasma gondii meets the challenge. Publ Libr Sci Pathog 8:e1002794Google Scholar
  47. Derouin F, Santillana-Hayat M (2000) Anti-toxoplasma activities of antiretroviral drugs and interactions with pyrimethamine and sulfadiazine in vitro. Antimicrob Agents Chemother 44(9):2575–2577CrossRefPubMedPubMedCentralGoogle Scholar
  48. Desolme B, Mévélec MN, Buzoni-Gatel D et al (2000) Induction of protective immunity against toxoplasmosis in mice by DNA immunization with a plasmid encoding Toxoplasma gondii GRA4 gene. Vaccine 18(23):2512–2521CrossRefPubMedGoogle Scholar
  49. Dhama K, Rajagunalan S, Chakraborty S et al (2013) Food-borne pathogens of animal origin-diagnosis, prevention, control and their zoonotic significance: a review. Pak J Biol Sci 16(20):1076–1085CrossRefPubMedGoogle Scholar
  50. Dickerson FB, Stallings CR, Boronow JJ et al (2009) A double-blind trial of adjunctive azithromycin in individuals with schizophrenia who are seropositive for Toxoplasma gondii. Schizophr Res 112(1–3):198–199. Scholar
  51. Długonska H (2014) Toxoplasma gondii and the host cells. Ann Parasitol 60(2):83–88PubMedGoogle Scholar
  52. Du J, An R, Chen L et al (2014) Toxoplasma gondii virulence factor ROP18 inhibits the host NF-κB pathway by promoting p65 degradation. J Biol Chem 289(18):12578–12592. Scholar
  53. Dubey JP (1982) Repeat transplacental transfer of Toxoplasma gondii in dairy goats. J Am Vet Med Assoc 180(10):1220–1221PubMedGoogle Scholar
  54. Dubey JP, Brown CA, Carpenter JL et al (1992) Fatal toxoplasmosis in domestic rabbits in the USA. Vet Parasitol 44(3–4):305–309CrossRefPubMedGoogle Scholar
  55. Dubey JP (1996) Infectivity and pathogenicity of Toxoplasma gondii oocysts for cats. J Parasitol 82(6):957–961CrossRefPubMedGoogle Scholar
  56. Dubey JP (2007) The history and life cycle of Toxoplasma gondii. In: Weiss LM, Kim K (ed) Toxoplasma gondii. The model apicomplexan: perspectives and methods. Academic Press, New York, pp 1–1Google Scholar
  57. Dubey JP (2008) The history of Toxoplasma gondii-the first 100 years. J Eukaryot Microbiol 55(6):467–475. Scholar
  58. Dubey JP (2009) Toxoplasmosis in pigs–the last 20 years. Vet Parasitol 164(2–4):89–103. Scholar
  59. Dubey JP, Lindsay DS, Lappin MR (2009) Toxoplasmosis and other intestinal coccidial infections in cats and dogs. Vet Clin North Am Small Anim Pract 39(6):1009–1034. Scholar
  60. Dubey JP, Passos LM, Rajendran C et al (2011) Isolation of viable Toxoplasma gondii from feral guinea fowl (Numida meleagris) and domestic rabbits (Oryctolagus cuniculus) from Brazil. J Parasitol 97(5):842–845. Scholar
  61. Dubey JP, Verma SK, Villena I et al (2016) Toxoplasmosis in the Caribbean islands: literature review, seroprevalence in pregnant women in ten countries, isolation of viable Toxoplasma gondii from dogs from St. Kitts, West Indies with report of new T. gondii genetic types. Parasitol Res 115(4):1627–1634. Scholar
  62. Dunn D, Wallon M, Peyron F, Petersen E, Peckham C, Gilbert R (1999) Mother-to-child transmission of toxoplasmosis: risk estimates for clinical counselling. Lancet 353(9167):1829–1833CrossRefPubMedGoogle Scholar
  63. Dupont CD, Christian DA, Hunter CA (2012) Immune response and immunopathology during toxoplasmosis. Semin Immunopathol 34(6):793–813. Scholar
  64. Elsheikha HM, Büsselberg D, Zhu XQ (2016) The known and missing links between Toxoplasma gondii and schizophrenia. Metab Brain Dis 31(4):749–759. Scholar
  65. Esch KJ1, Petersen CA (2013) Transmission and epidemiology of zoonotic protozoal diseases of companion animals. Clin Microbiol Rev 26(1):58–85. Scholar
  66. Elbez-Rubinstein A, Ajzenberg D, Dardé ML et al (2009) Congenital toxoplasmosis and reinfection during pregnancy: case report, strain characterization, experimental model of reinfection, and review. J Infect Dis 199(2):280–285CrossRefPubMedGoogle Scholar
  67. Emery S, Kelleher AD, Workman C et al (2007) Influence of IFNgamma co-expression on the safety and antiviral efficacy of recombinant fowlpox virus HIV therapeutic vaccines following interruption of antiretroviral therapy. Hum Vaccin 3(6):260–267CrossRefPubMedGoogle Scholar
  68. Ferguson DJ, Hutchison WM (1987) An ultrastructural study of the early development and tissue cyst formation of Toxoplasma gondii in the brains of mice. Parasitol Res 73(6):483–491CrossRefPubMedGoogle Scholar
  69. Ferraro G, Laguía Becher M, Angel SO et al (2008) Efficient expression of a Toxoplasma gondii dense granule Gra4 antigen in tobacco leaves. Exp Parasitol 120:118–122. Scholar
  70. Feustel SM, Meissner M, Liesenfeld O (2012) Toxoplasma gondii and the blood-brain barrier. Virulence 3(2):182–192. Scholar
  71. Frenkel JK, Dubey JP, Miller NL (1970) Toxoplasma gondii in cats: fecal stages identified as coccidian oocysts. Science 167:893–896CrossRefPubMedGoogle Scholar
  72. Fricker-Hidalgo H, Cimon B, Chemla C et al (2013) Toxoplasma seroconversion with negative or transient immunoglobulin M in pregnant women: myth or reality? A French multicenter retrospective study. J Clin Microbiol 51(7):2103–2111. Scholar
  73. Ganapathy M1, Perumal A, Mohan C et al (2014) Immunogenicity of Brugia malayi Abundant Larval Transcript-2, a potential filarial vaccine candidate expressed in tobacco. Plant Cell Rep 33(1):179–188. Scholar
  74. Garcia JL, Innes EA, Katzer F (2014) Current progress toward vaccines against Toxoplasma gondii. Vaccine: Develop Ther 4:23–37Google Scholar
  75. Gazzinelli RT, Eltoum I, Wynn TA et al (1993) Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol 151(7):3672–3681PubMedGoogle Scholar
  76. Gilbert R, Gras L (2003) European multicentre study on congenital toxoplasmosis. Effect of timing and type of treatment on the risk of mother to child transmission of Toxoplasma gondii. BJOG 110(2):112–120CrossRefPubMedGoogle Scholar
  77. Glasner PD, Silveira C, Kruszon-Moran D et al (1992) An unusually high prevalence of ocular toxoplasmosis in southern Brazil. Am J Ophthalmol 114(2):136–144CrossRefPubMedGoogle Scholar
  78. Gómez E, Chimeno Zoth S, Carrillo E et al (2008) Mucosal immunity induced by orally administered transgenic plants. Immunobiology 213(8):671–675. Scholar
  79. Gonzalez-Rabade N, McGowan EG, Zhou F et al (2011) Immunogenicity of chloroplast-derived HIV-1 p24 and a p24-Nef fusion protein following subcutaneous and oral administration in mice. Plant Biotechnol J 9(6):629–638. Scholar
  80. Granell A, Fernández del-Carmen A, Orzáez D (2010) In planta production of plant-derived and non-plant-derived adjuvants. Expert Rev Vaccines 9(8):843–858. Scholar
  81. Gras L, Wallon M, Pollak A et al (2005) Association between prenatal treatment and clinical manifestations of congenital toxoplasmosis in infancy: a cohort study in 13 European centres. Acta Paediatr 94(12):1721–1731CrossRefPubMedGoogle Scholar
  82. Guo M, Dubey JP, Hill D et al (2015) Prevalence and risk factors for Toxoplasma gondii infection in meat animals and meat products destined for human consumption. J Food Prot 78(2):457–476. Scholar
  83. Halonen SK1, Weiss LM (2013) Toxoplasmosis. Handb Clin Neurol 114:125–145.
  84. Harning D, Spenter J, Metsis A et al (1996) Recombinant Toxoplasma gondii surface antigen 1 (P30) expressed in Escherichia coli is recognized by human Toxoplasma-specific immunoglobulin M (IgM) and IgG antibodies. Clin Diagn Lab Immunol 3(3):355–357PubMedPubMedCentralGoogle Scholar
  85. Harker KS, Ueno N, Lodoen MB (2015) Toxoplasma gondii dissemination: a parasite’s journey through the infected host. Parasite Immunol 37(3):141–149. Scholar
  86. Hayden CA, Egelkrout EM, Moscoso AM et al (2012) Production of highly concentrated, heat-stable hepatitis B surface antigen in maize. Plant Biotechnol J 10(8):979–984. Scholar
  87. Hennequin C, Dureau P, N’Guyen L et al (1997) Congenital toxoplasmosis acquired from an immune woman. Pediatr Infect Dis J 16(1):75–77CrossRefPubMedGoogle Scholar
  88. Hernandez M, Rosas G, Cervantes J et al (2014) Transgenic plants: a 5-year update on oral antipathogen vaccine development. Expert Rev Vaccines 13(12):1523–1536. Scholar
  89. Hiszczynska-Sawicka E, Gatkowska JM, Grzybowski MM et al (2014) Veterinary vaccines against toxoplasmosis. Parasitology 141(11):1365–1378. Scholar
  90. Holland GN (2003) Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease. Am J Ophthalmol 136(6):973–988CrossRefPubMedGoogle Scholar
  91. Hu K, Johnson J, Florens L et al (2006) Cytoskeletal components of an invasion machine-the apical complex of Toxoplasma gondii. PLoS Pathog 2(2):e13. Scholar
  92. Innes EA, Vermeulen AN (2006) Vaccination as a control strategy against the coccidial parasites Eimeria Toxoplasma and Neospora. Parasitology 133(Suppl):S145–S168CrossRefPubMedGoogle Scholar
  93. Innes EA (2010) Vaccination against Toxoplasma gondii: an increasing priority for collaborative research? Expert Rev Vaccines 9(10):1117–1119. Scholar
  94. Israelski DM, Remington JS (1993) Toxoplasmosis in the non-AIDS immunocompromised host. Curr Clin Top Infect Dis 13:322–356Google Scholar
  95. Jacob SS, Cherian S, Sumithra TG et al (2013) Edible vaccines against veterinary parasitic diseases—current status and future prospects. Vaccine 31(15):1879–1885. Scholar
  96. Jasper S, Vedula SS, John SS et al (2017) Corticosteroids as adjuvant therapy for ocular toxoplasmosis. Cochrane Database Syst Rev 1:CD007417.
  97. Jiang HH, Li MW, Xu MJ et al (2015) Prevalence of Toxoplasma gondii in dogs in Zhanjiang, Southern China. Korean J Parasitol 53(4):493–496. Scholar
  98. Jones JL, Dargelas V, Roberts J et al (2009) Risk factors for Toxoplasma gondii infection in the United States. Clin Infect Dis 49(6):878–884. Scholar
  99. Jongert E, Roberts CW, Gargano N (2009) Vaccines against Toxoplasma gondii: challenges and opportunities. Mem Inst Oswaldo Cruz 104(2):252–266. Erratum in: Mem Inst Oswaldo Cruz. 2010 Feb; 105CrossRefPubMedGoogle Scholar
  100. Kapusta J, Pniewski T, Wojciechowicz J et al (2010) Nanogram doses of alum-adjuvanted HBs antigen induce humoral immune response in mice when orally administered. Arch Immunol Ther Exp (Warsz) 58(2):143–151. Scholar
  101. Katzer F, Brülisauer F, Collantes-Fernández E et al (2011) Increased Toxoplasma gondii positivity relative to age in 125 Scottish sheep flocks; evidence of frequent acquired infection. Vet Res 42:121. Scholar
  102. Kesik-Brodacka M, Lipiec A, Kozak Ljunggren M et al (2017) Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae. PLoS Negl Trop Dis 11(3):e0005451. Scholar
  103. Khan IA, Smith KA, Kasper LH (1988) Induction of antigen-specific parasiticidal cytotoxic T cell splenocytes by a major membrane protein (P30) of Toxoplasma gondii. J Immunol 141(10):3600–3605PubMedGoogle Scholar
  104. Khan IA, Murphy PM, Casciotti L et al (2001) Mice lacking the chemokine receptor CCR1 show increased susceptibility to Toxoplasma gondii infection. J Immunol 166(3):1930–1937CrossRefPubMedGoogle Scholar
  105. Khurana S, Batra N (2016) Toxoplasmosis in organ transplant recipients: evaluation, implication, and prevention. Trop Parasitol 6(2):123–128CrossRefPubMedPubMedCentralGoogle Scholar
  106. Kieffer F, Wallon M (2013) Congenital toxoplasmosis. Handb Clin Neurol 112:1099–1101. Scholar
  107. Kim JY, Ahn MH, Jun HS et al (2006) Toxoplasma gondii inhibits apoptosis in infected cells by caspase inactivation and NF-kappaB activation. Yonsei Med J 47(6):862–869CrossRefPubMedPubMedCentralGoogle Scholar
  108. Kim SK, Fouts AE, Boothroyd JC (2007) Toxoplasma gondii dysregulates IFN-gamma-inducible gene expression in human fibroblasts: insights from a genome-wide transcriptional profiling. J Immunol 178(8):5154–5165CrossRefPubMedGoogle Scholar
  109. Kim JH, Kang KI, Kang WC et al (2009) Porcine abortion outbreak associated with Toxoplasma gondii in Jeju Island. Korea J Vet Sci 10:147–151CrossRefPubMedGoogle Scholar
  110. Kong Q, Richter L, Yang YF (2001) Oral immunization with hepatitis B surface antigen expressed in transgenic plants. Proc Natl Acad Sci U S A 98(20):11539115–11539144CrossRefGoogle Scholar
  111. Kostrzak A, Cervantes Gonzalez M, Guetard D et al (2009) Oral administration of low doses of plant-based HBsAg induced antigen-specific IgAs and IgGs in mice, without increasing levels of regulatory T cells. Vaccine 27(35):4798–47807. Scholar
  112. Labruyere E, Lingnau M, Mercier C et al (1999) Differential membrane targeting of the secretory proteins GRA4 and GRA6 within the parasitophorous vacuole formed by Toxoplasma gondii. Mol Biochem Parasitol 20;102(2):311–324CrossRefPubMedGoogle Scholar
  113. Laguía-Becher M, Martín V, Kraemer M et al (2010) Effect of codon optimization and subcellular targeting on Toxoplasma gondii antigen SAG1 expression in tobacco leaves to use in subcutaneous and oral immunization in mice. BMC Biotechnol 10:52. Scholar
  114. Langermans JA, van der Hulst ME, Nibbering PH et al (1992) Endogenous tumor necrosis factor alpha is required for enhanced antimicrobial activity against Toxoplasma gondii and Listeria monocytogenes in recombinant gamma interferon-treated mice. Infect Immun 60(12):5107–5112PubMedPubMedCentralGoogle Scholar
  115. Licciardi PV, Underwood JR (2011) Plant-derived medicines: a novel class of immunological adjuvants. Int Immunopharmacol 11(3):390–398. Scholar
  116. Limaye A, Koya V, Samsam M et al (2006) Receptor-mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system. FASEB J 20(7):959–961CrossRefPubMedPubMedCentralGoogle Scholar
  117. Lim SS, Othman RY (2014) Recent advances in Toxoplasma gondii immunotherapeutics. Korean J Parasitol 52(6):581–593. Scholar
  118. Lindsay DS, Dubey JP (2011) Toxoplasma gondii: the changing paradigm of congenital toxoplasmosis. Parasitology 138(14):1829–1831. Scholar
  119. Machacova T, Bartova E, Sedlak K (2016) Seroprevalence and risk factors of infections with Neospora caninum and Toxoplasma gondii in hunting dogs from Campania region, southern Italy. Folia Parasitol (Praha) 6;63. pii:2016.012.
  120. Magalhães FJ, Ribeiro-Andrade M, Souza FM et al (2017) Seroprevalence and spatial distribution of Toxoplasma gondii infection in cats, dogs, pigs and equines of the Fernando de Noronha Island. Brazil Parasitol Int 66(2):43–46. Scholar
  121. Makioka A, Kobayashi A (1991) Toxoplasmacidal activity of macrophages activated by recombinant major surface antigen (P30) of Toxoplasma gondii. Infect Immun 59(8):2851–2852PubMedPubMedCentralGoogle Scholar
  122. Marchioro AA, Tiyo BT, Colli CM et al (2016) First Detection of Toxoplasma gondii DNA in the fresh leafs of vegetables in South America. Vector Borne Zoonotic Dis 16(9):624–626. Scholar
  123. Martin V, Supanitsky A, Echeverria P et al (2004) Recombinant GRA4 or ROP2 protein combined with alum or the gra4 gene provides partial protection in chronic murine models of toxoplasmosis. Clin Lab Immunol 11:704–710CrossRefGoogle Scholar
  124. Mason HS, Herbst-Kralovetz MM (2012) Plant-derived antigens as mucosal vaccines. Curr Top Microbiol Immunol 354:101–120. Scholar
  125. Mastropaolo JP, Moskowitz KH, Dacanay RJ et al (1989) Conditioned taste aversions as a behavioral baseline for drug discrimination learning: an assessment with phencyclidine. Pharmacol Biochem Behav 32(1):1–8CrossRefPubMedGoogle Scholar
  126. Matias M, Gomes A, Marques T, Fonseca AC (2014) Ocular toxoplasmosis: a very rare presentation in an immunocompetent patient. BMJ Case Rep. Scholar
  127. Matsumoto Y, Suzuki S, Nozoye T et al (2009) Oral immunogenicity and protective efficacy in mice of transgenic rice plants producing a vaccine candidate antigen (As16) of Ascaris suum fused with cholera toxin B subunit. Transgenic Res 18(2):185–192. Scholar
  128. McGettigan BD, Hew M, Phillips E et al (2012) Sulphadiazine-induced renal stones in a 63-year-old HIV-infected man treated for toxoplasmosis. BMJ Case Rep pii:bcr2012006638.
  129. Melzer T, Duffy A, Weiss LM et al (2008) The gamma interferon (IFN-gamma)-inducible GTP-binding protein IGTP is necessary for toxoplasma vacuolar disruption and induces parasite egression in IFN-gamma-stimulated astrocytes. Infect Immun 76(11):4883–4894.
  130. Mennechet FJ, Kasper LH, Rachinel N et al (2004) Intestinal intraepithelial lymphocytes prevent pathogen-driven inflammation and regulate the Smad/T-bet pathway of lamina propria CD4+ T cells. Eur J Immunol 34(4):1059–1067CrossRefPubMedGoogle Scholar
  131. Menzies FM, Henriquez FL, Roberts CW (2008) Immunological control of congenital toxoplasmosis in the murine model. Immunol Lett 115(2):83–89CrossRefPubMedGoogle Scholar
  132. Mévélec MN, Mercereau-Puijalon O, Buzoni-Gatel D et al (1998) Mapping of B epitopes in GRA4, a dense granule antigen of Toxoplasma gondii and protection studies using recombinant proteins administered by the oral route. Parasite Immunol 20(4):183–195PubMedGoogle Scholar
  133. Mévélec MN, Bout D, Desolme B et al (2005) Evaluation of protective effect of DNA vaccination with genes encoding antigens GRA4 and SAG1 associated with GM-CSF plasmid, against acute, chronical and congenital toxoplasmosis in mice. Vaccine 23:4489–4499CrossRefPubMedGoogle Scholar
  134. Miller CM, Boulter NR, Ikin RJ, Smith NC (2009) The immunobiology of the innate response to Toxoplasma gondii. Int J Parasitol 39(1):23–39. Scholar
  135. Molestina RE, Payne TM, Coppens I et al (2003) Activation of NF-kappaB by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated IkappaB to the parasitophorous vacuole membrane. J Cell Sci 116(Pt 21):4359–4371CrossRefPubMedGoogle Scholar
  136. Moncada PA, Montoya JG (2012) Toxoplasmosis in the fetus and newborn: an update on prevalence, diagnosis and treatment. Expert Rev Anti Infect Ther 10(7):815–828. Scholar
  137. Monreal-Escalante E, Govea-Alonso DO, Hernández M et al (2016) Towards the development of an oral vaccine against porcine cysticercosis: expression of the protective HP6/TSOL18 antigen in transgenic carrots cells. Planta 243(3):675–685. Scholar
  138. Montazeri M, Sharif M, Sarvi S et al (2017) A systematic review of in vitro and in vivo activities of anti-Toxoplasma drugs and compounds (2006-2016). Front Microbio 8:25. Scholar
  139. Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363(9425):1965–1976CrossRefPubMedGoogle Scholar
  140. Muñoz M, Liesenfeld O, Heimesaat MM (2011) Immunology of Toxoplasma gondii. Immunol Rev 240(1):269–285. Scholar
  141. Nicolle C, Manceaux L (1908) Sur une infection à corps de Leishman (ou organismes voisins) du gondi. C R Hebd Seances Acad Sci 147:763–766Google Scholar
  142. Nigro M, Gutierrez A, Hoffer AM et al (2003) Evaluation of Toxoplasma gondii recombinant proteins for the diagnosis of recently acquired toxoplasmosis by an immunoglobulin G analysis. Diagn Microbiol Infect Dis 47:609–613CrossRefPubMedGoogle Scholar
  143. Okamoto N, Keeling PJ (2014) The 3D structure of the apical complex and association with the flagellar apparatus revealed by serial TEM tomography in Psammosa pacifica, a distant relative of the Apicomplexa. PLoS ONE 9(1):e84653. Scholar
  144. Paul M, Ma JK (2010) Plant-made immunogens and effective delivery strategies. Expert Rev Vaccines 9(8):821–833. Scholar
  145. Peng HJ, Chen XG, Lindsay DS (2011) A review: competence, compromise, and concomitance-reaction of the host cell to Toxoplasma gondii infection and development. J Parasitol 97(4):620–628. Scholar
  146. Perkins ES (1973) Ocular toxoplasmosis. Br J Ophthalmol 57(1):1–17CrossRefPubMedPubMedCentralGoogle Scholar
  147. Pleyer U, Schlüter D, Mänz M (2014) Ocular toxoplasmosis: recent aspects of pathophysiology and clinical implications. Ophthalmic Res 52(3):116–123. Scholar
  148. Pollard AM, Onatolu KN, Hiller L et al (2008) Highly polymorphic family of glycosylphosphatidylinositol-anchored surface antigens with evidence of developmental regulation in Toxoplasma gondii. Infect Immun 76(1):103–110CrossRefPubMedGoogle Scholar
  149. Raeghi S, Akaberi A, Sedeghi S (2011) Seroprevalence of Toxoplasma gondii in sheep, cattle and horses in Urmia North-West of Iran. Iran J Parasitol 6(4):90–94PubMedPubMedCentralGoogle Scholar
  150. Rajapakse R, Uring-Lambert B, Andarawewa KL (2007) 1,25(OH)2D3 inhibits in vitro and in vivo intracellular growth of apicomplexan parasite Toxoplasma gondii. J Steroid Biochem Mol Biol 103(3–5):811–814CrossRefPubMedGoogle Scholar
  151. Reichmann G, Walker W, Villegas EN (2000) The CD40/CD40 ligand interaction is required for resistance to toxoplasmic encephalitis. Infect Immun 68(3):1312–1318CrossRefPubMedPubMedCentralGoogle Scholar
  152. Rodriguez JB, Szajnman SH (2012) New antibacterials for the treatment of toxoplasmosis; a patent review. Expert Opin Ther Pat 22(3):311–333. Scholar
  153. Robert-Gangneux F, Dardé ML (2012) Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 25(2):264–96. doi:0.1128/CMR.05013-11. Erratum in: Clin Microbiol Rev 2012 25(3):583Google Scholar
  154. Rosales-Mendoza S, Salazar-González JA (2014) Immunological aspects of using plant cells as delivery vehicles for oral vaccines. Expert Rev Vaccines 13(6):737–749. Scholar
  155. Rosso F, Les JT, Agudelo A et al (2008) Prevalence of infection with Toxoplasma gondii among pregnant women in Cali, Colombia, South America. Am J Trop Med Hyg 78(3):504–508PubMedCrossRefGoogle Scholar
  156. Rostami A, Seyyedtabaei SJ, Aghamolaie S et al (2016) Seroprevalence and risk factors associated with Toxoplasma gondii infection among rural communities in northern Iran. Rev Inst Med Trop Sao Paulo 22(58):70. Scholar
  157. Sathish K, Sriraman R, Subramanian BM et al (2012) Plant expressed coccidial antigens as potential vaccine candidates in protecting chicken against coccidiosis. Vaccine 30(30):4460–4464. Scholar
  158. Saeij JP, Coller S, Boyle JP et al (2007) Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445(7125):324–327CrossRefPubMedGoogle Scholar
  159. Sánchez VR, Pitkowski MN, Fernández Cuppari AV, Rodríguez FM, Fenoy IM, Frank FM, Goldman A, Corral RS, Martin V (2011) Combination of CpG-oligodeoxynucleotides with recombinant ROP2 or GRA4 proteins induces protective immunity against Toxoplasma gondii infection. Exp Parasitol 128(4):448–453. Scholar
  160. Sanecka A, Frickel EM (2012) Use and abuse of dendritic cells by Toxoplasma gondii. Virulence 3(7):678–689. Scholar
  161. Santi L, Batchelor L, Huang Z et al (2008) An efficient plant viral expression system generating orally immunogenic Norwalk virus-like particles. Vaccine 26(15):1846–1854. Scholar
  162. Scallan E, Hoekstra RM, Angulo FJ et al (2011) Foodborne illness acquired in the United States-major pathogens. Emerg Infect Dis 17:7–15CrossRefPubMedPubMedCentralGoogle Scholar
  163. Shaapan RM (2016) The common zoonotic protozoal diseases causing abortion. J Parasit Dis 40(4):1116–1129CrossRefPubMedGoogle Scholar
  164. Shapira S, Harb OS, Margarit J et al (2005) Initiation and termination of NF-kappaB signaling by the intracellular protozoan parasite Toxoplasma gondii. J Cell Sci 118(Pt 15):3501–3508CrossRefPubMedGoogle Scholar
  165. Shibre T, Alem A, Abdulahi A et al (2010) Trimethoprim as adjuvant treatment in schizophrenia: a double-blind, randomized, placebo-controlled clinical trial. Schizophr Bull 36(4):846–851. Scholar
  166. Siachoque H, Guzman F, Burgos J et al (2006) Toxoplasma gondii: immunogenicity and protection by P30 peptides in a murine model. Exp Parasitol 114(1):62–65CrossRefPubMedGoogle Scholar
  167. Sibley LD, Adams LB, Fukutomi Y et al (1991) Tumor necrosis factor-alpha triggers antitoxoplasmal activity of IFN-gamma primed macrophages. J Immunol 147(7):2340–2345PubMedGoogle Scholar
  168. Sibley LD (2011) Invasion and intracellular survival by protozoan parasites. Immunol Rev 240(1):72–91. Scholar
  169. Skariah S, McIntyre MK, Mordue DG (2010) Toxoplasma gondii: determinants of tachyzoite to bradyzoite conversion. Parasitol Res 107(2):253–260. Scholar
  170. Sturge CR, Yarovinsky F (2014) Complex immune cell interplay in the gamma interferon response during Toxoplasma gondii infection. Infect Immun 82(8):3090–3097. Scholar
  171. Suzuki Y, Conley FK, Remington JS (1989) Importance of endogenous IFN-gamma for prevention of toxoplasmic encephalitis in mice. J Immunol 143(6):2045–2050PubMedGoogle Scholar
  172. Suzuki Y, Remington JS (1993) Toxoplasmic encephalitis in AIDS patients and experimental models for study of the disease and its treatment. Res Immunol 144(1):66–67CrossRefPubMedGoogle Scholar
  173. Tenter AM, Heckeroth AR, Weiss LM (2000) Toxoplasma gondii: from animals to humans. Int J Parasitol 30(12–13):1217–1258. Erratum in: Int J Parasitol 2001 31(2):217–220Google Scholar
  174. Thiébaut R, Leproust S, Chêne G et al (2007) Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients’ data. Lancet 369(9556):115–122CrossRefPubMedGoogle Scholar
  175. Torgerson PR, Mastroiacovo P (2013) The global burden of congenital toxoplasmosis: a systematic review. Bull World Health Organ 91(7):501–508. Scholar
  176. Torrey EF, Yolken RH (2003) Toxoplasma gondii and schizophrenia. Emerg Infect Dis 9(11):1375–1380CrossRefPubMedPubMedCentralGoogle Scholar
  177. Vajdy M (2011) Immunomodulatory properties of vitamins, flavonoids and plant oils and their potential as vaccine adjuvants and delivery systems. Expert Opin Biol Ther 11(11):1501–1513. Scholar
  178. Vaudaux JD, Muccioli C, James ER et al (2010) Identification of an atypical strain of Toxoplasma gondii as the cause of a waterborne outbreak of toxoplasmosis in Santa Isabel do Ivai, Brazil. J Infect Dis 202(8):1226–1233CrossRefPubMedPubMedCentralGoogle Scholar
  179. Wang Y, Wang G, Zhang D et al (2013) Screening and identification of novel B cell epitopes of Toxoplasma gondii SAG1. Parasit Vectors 6:125. Scholar
  180. Wang Y, Yin H (2014) Research progress on surface antigen 1 (SAG1) of Toxoplasma gondii. Parasit Vectors 7:180. Scholar
  181. Wiengcharoen J, Thompson RC, Nakthong C et al (2011) Transplacental transmission in cattle: is Toxoplasma gondii less potent than Neospora caninum? Parasitol Res 108(5):1235–1241. Scholar
  182. Wilbers RH, Westerhof LB, van Noort K et al (2017) Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants. Sci Rep 7:45910. Scholar
  183. Wilson CB, Remington JS, Stagno S et al (1980) Development of adverse sequelae in children born with subclinical congenital Toxoplasma infection. Pediatrics 66(5):767–774PubMedGoogle Scholar
  184. Xiao J, Yolken RH (2015) Strain hypothesis of Toxoplasma gondii infection on the outcome of human diseases. Acta Physiol (Oxf) 213(4):828–845. Scholar
  185. Yarovinsky F, Hieny S, Sher A (2008) Recognition of Toxoplasma gondii by TLR11 prevents parasite-induced immunopathology. J Immunol 181(12):8478–8484CrossRefPubMedPubMedCentralGoogle Scholar
  186. Yusibov V, Rabindran S (2008) Recent progress in the development of plant derived vaccines. Expert Rev Vaccines 7(8):1173–1183. Scholar
  187. Yusibov V, Streatfield SJ, Kushnir N (2011) Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond. Hum Vaccin 7(3):313–321CrossRefPubMedGoogle Scholar
  188. Zhang H, Liu M, Li Y et al (2010) Oral immunogenicity and protective efficacy in mice of a carrot-derived vaccine candidate expressing UreB subunit against Helicobacter pylori. Protein Expr Purif 69(2):127–131. Scholar
  189. Zhang NZ, Chen J, Wang M (2013) Vaccines against Toxoplasma gondii: new developments and perspectives. Expert Rev Vaccines 12(11):1287–1299. Scholar
  190. Zhang NZ, Wang M, Xu Y (2015) Recent advances in developing vaccines against Toxoplasma gondii: an update. Expert Rev Vaccines 14(12):1609–1621. Scholar
  191. Zhu S (2009) Psychosis may be associated with toxoplasmosis. Med Hypotheses 3(5):799–801. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Valeria Sander
    • 1
  • Sergio O. Angel
    • 1
  • Marina Clemente
    • 1
    Email author
  1. 1.Instituto Tecnológico Chascomús, IIB-INTECH, CONICET-UNSAMChascomúsArgentina

Personalised recommendations