Advertisement

Medical Microbiology and Immunology

, Volume 203, Issue 5, pp 315–322 | Cite as

Th1 and Th2 immune response to P30 and ROP18 peptides in human toxoplasmosis

  • Elizabeth Torres-Morales
  • Laura Taborda
  • Nestor Cardona
  • Alejandra De-la-Torre
  • Juan Carlos Sepulveda-Arias
  • Manuel Alfonso Patarroyo
  • Jorge Enrique Gomez-MarinEmail author
Original Investigation

Abstract

We determined the specific lymphocyte proliferative response and cytokine profile production regarding Toxoplasma P30 (2017 from virulent and non-virulent strain) and ROP18 protein-derived peptides (from clonal lineages I, II and III) in 19 patients having ocular toxoplasmosis, five suffering chronic asymptomatic infection, nine with congenital toxoplasmosis and eight Toxoplasma negative people. A Beckman Coulter FC500 flow cytometer was used for determining antigen-specific T cells (CD3+ CD4+ or CD3+ CD8+ cells) in peripheral blood culture. IFN γ and IL10 levels were determined in culture supernatants. Specific CD4+ and CD8+ T cell response to total antigen and P30- and ROP18-derived peptides was observed in infected people. Ocular toxoplasmosis patients had a preferential Th2 response after antigenic stimulation. Non-virulent peptide 2017 was able to shift response toward Th1 in congenitally infected children and virulent peptide 2017 induced a Th2 response in chronically infected, asymptomatic people. An immune response in human toxoplasmosis after ex vivo antigenic stimulation was Th1- or Th2-skewed, depending on a patient’s clinical condition. Colombian ocular toxoplasmosis patients’ immune response was Th2-skewed, regardless of the nature of antigen stimulus.

Keywords

Toxoplasma P30 protein ROP18 Interferon gamma IL10 Th1 Th2 Peptides Vaccine 

Notes

Acknowledgments

Financed by grants 111351929258 from Colciencias (Colombian Scientific Government Agency) and 5-09-3 from the Universidad Tecnológica de Pereira.

References

  1. 1.
    Gómez-Marin JE (2010) Toxoplasmosis. In: Gomez-Marin JE. Protozoologia médica: Protozoos parásitos en el contexto latinoamericano, 1st ed. Editorial Manual Moderno, Bogotá, p 65Google Scholar
  2. 2.
    Robertson LJ, van der Giessen JW, Batz MB, Kojima M, Cahill S (2013) Have foodborne parasites finally become a global concern? Trends Parasitol 29:101–103PubMedCrossRefGoogle Scholar
  3. 3.
    Gómez-Marin J, de-la-Torre A, Angel-Muller E, Rubio J et al (2011) First Colombian multicentric newborn screening for congenital toxoplasmosis. PLoS Negl Trop Dis 5(5):e1195PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Fatoohi AF, Cozon GJ, Greenland T, Ferrandiz J, Bienvenu J, Picot S, Peyron F (2002) Cellular immune responses to recombinant antigens in pregnant women chronically infected with Toxoplasma gondii. Clin Diagn Lab Immunol 9:704–707PubMedPubMedCentralGoogle Scholar
  5. 5.
    Mendes ÉA, Fonseca FG, Casério BM, Colina JP, Gazzinelli RT, Caetano BC (2013) Recombinant vaccines against T. gondii: comparison between homologous and heterologous vaccination protocols using two viral vectors expressing SAG1. PLoS One 8(5):e63201PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Siachoque H, Guzman F, Burgos J, Patarroyo ME, Gomez-Marin JE (2006) Toxoplasma gondii: immunogenicity and protection by P30 peptides in a murine model. Exp Parasitol 114:62–65PubMedCrossRefGoogle Scholar
  7. 7.
    Tao Q, Fang R, Zhang W, Wang Y, Cheng J, Li Y, Fang K, Khan MK, Hu M, Zhou Y, Zhao J (2013) Protective immunity induced by a DNA vaccine-encoding Toxoplasma gondii microneme protein 11 against acute toxoplasmosis in BALB/c mice. Parasitol Res 112:2871–2877PubMedCrossRefGoogle Scholar
  8. 8.
    Qu D, Han J, Du A (2013) Evaluation of protective effect of multiantigenic DNA vaccine encoding MIC3 and ROP18 antigen segments of Toxoplasma gondii in mice. Parasitol Res 112:2593–2599PubMedCrossRefGoogle Scholar
  9. 9.
    Sepulveda-Arias JC, Kempf MC, Wiehr S, Wedekind D, Hedrich HJ, Gross U, Herrmann T (2008) Control of Toxoplasma gondii infection by athymic LEW-Whn rnu rats. Parasite Immunol 30:323–333PubMedCrossRefGoogle Scholar
  10. 10.
    Feliu V, Vasseur V, Grover HS, Chu HH, Brown MJ, Wang J, Boyle JP, Robey EA, Shastri N, Blanchard N (2013) Location of the CD8 T cell epitope within the antigenic precursor determines immunogenicity and protection against the Toxoplasma gondii parasite. PLoS Pathog 9(6):e1003449PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Tan TG, Mui E, Cong H et al (2010) Identification of T. gondii epitopes, adjuvants, and host genetic factors that influence protection of mice and humans. Vaccine 28:3977–3989PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Cong H, Mui EJ, Witola WH et al (2012) Toxoplasma gondii HLA-B*0702-restricted GRA7(20-28) peptide with adjuvants and a universal helper T cell epitope elicits CD8(+) T cells producing interferon-gamma and reduces parasite burden in HLA-B*0702 mice. Human Immunol 73:1–10CrossRefGoogle Scholar
  13. 13.
    de-la-Torre A, Lopez-Castillo C, Gomez-Marin JE (2009) Incidence and clinical characteristics in a Colombian cohort of ocular toxoplasmosis. Eye 23:1090–1093PubMedCrossRefGoogle Scholar
  14. 14.
    Cardona N, de-la-Torre A, Siachoque H, Patarroyo MA, Gomez-Marin JE (2009) Toxoplasma gondii: P30 peptides recognition pattern in human toxoplasmosis. Exp Parasitol 123:199–202PubMedCrossRefGoogle Scholar
  15. 15.
    Taylor S, Barragan A, Su C et al (2006) A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 314:1776–1780PubMedCrossRefGoogle Scholar
  16. 16.
    Kahi S, Cozon GJN, Greenland T, Wallon M, Gay-Andrieu F, Peyron F (1998) Rapid flow cytometric method to explore cellular immunity against Toxoplasma gondii in humans. Clin Diag Lab Immunol 5:745–748Google Scholar
  17. 17.
    Fatoohi F, Cozon GJ, Wallon M, Kodjikian L, Peyron F (2006) Systemic T cell response to Toxoplasma gondii antigen in patients with ocular toxoplasmosis. Jpn J Ophthalmol 50:103–110PubMedCrossRefGoogle Scholar
  18. 18.
    de-la-Torre A, Sauer A, Bourcier T, Speeg-Schatz C, Ballonzoli L, Ajzenberg D, Sundar N, Grigg ME, Villard O, Brunet J, Pfaff A, Gomez-Marin J, Candolfi E (2013) Severe Southamerican ocular toxoplasmosis is associated with decreased IFN-gamma/IL-17A and increased IL-6/IL-13 intraocular levels. PLoS Neglected Trop Dis 7(11):e2541. doi: 10.1371/journal.pntd.0002541 CrossRefGoogle Scholar
  19. 19.
    Gallego C, Saavedra-Matiz C, Gómez-Marín JE (2006) Direct genotyping of animal and human isolates of Toxoplasma gondii from Colombia (South America). Acta Trop 97:161–167PubMedCrossRefGoogle Scholar
  20. 20.
    Sánchez V, de-la-Torre A, Gómez Marín JE (2014) Characterization of ROP18 alleles in human toxoplasmosis. Parasitol Int 63:463–469PubMedCrossRefGoogle Scholar
  21. 21.
    Morisset S, Peyron F, Lobry JR et al (2008) Serotyping of Toxoplasma gondii: striking homogeneous pattern between symptomatic and asymptomatic infections within Europe and South America. Microbes Infect 10:742–747PubMedCrossRefGoogle Scholar
  22. 22.
    Saeij JP, Coller S, Boyle JP, Jerome ME, White MW, Boothroyd JC (2007) Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445:324–327PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Kahi S, Cozon GJ, Pinon JM et al (1999) A switch towards Th2 during serological rebound in children with congenital toxoplasmosis. Clin Exp Immunol 117:524–528PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    McLeod R, Mack DG, Boyer K et al (1990) Phenotypes and functions of lymphocytes in congenital toxoplasmosis. J Lab Clin Med 116:623–635PubMedGoogle Scholar
  25. 25.
    D’Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G (1993) Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med 178:1041–1048PubMedCrossRefGoogle Scholar
  26. 26.
    Kato M, Claveria FG, Maki Y et al (2007) Reactivity of synthetic SAG1 (p30) peptide sequences with RH, S273 and Beverley strain-induced anti-Toxoplasma gondii antibodies. Pathobiology 74:50–56PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Elizabeth Torres-Morales
    • 1
  • Laura Taborda
    • 1
  • Nestor Cardona
    • 1
  • Alejandra De-la-Torre
    • 1
    • 2
  • Juan Carlos Sepulveda-Arias
    • 3
  • Manuel Alfonso Patarroyo
    • 2
    • 4
  • Jorge Enrique Gomez-Marin
    • 1
    Email author
  1. 1.Grupo de Estudio en Parasitología Molecular (GEPAMOL), Facultad de Ciencias de la Salud, Centro de Investigaciones BiomédicasUniversidad del QuindioArmeniaColombia, South America
  2. 2.Departamento de Ciencias BásicasUniversidad del RosarioBogotáColombia
  3. 3.Grupo Infección e Inmunidad, Facultad de Ciencias de la SaludUniversidad Tecnológica de PereiraPereiraColombia
  4. 4.Departamento de Biologia Molecular e InmunologiaFundacion Instituto de Inmunologia de Colombia (FIDIC)BogotáColombia

Personalised recommendations