Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Suppression of $CD4^+$ T-Cells in the Spleen of Mice Infected with Toxoplasma gondii KI-1 Tachyzoites

  • Kim, Won-Hee (Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center) ;
  • Shin, Eun-Hee (Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center) ;
  • Kim, Jae-Lip (Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center) ;
  • Yu, Seung-Young (Department of Ophthalmology, Kyung Hee University Graduate School of Medicine) ;
  • Jung, Bong-Kwang (Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center) ;
  • Chai, Jong-Yil (Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center)
  • Received : 2010.09.15
  • Accepted : 2010.10.22
  • Published : 2010.12.31
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Abstract

Toxoplasma gondii KI-1, a recent new isolate from Korea, shows similar pathogenicity and infectivity to mice compared to the virulent RH strain. To understand characteristics of host immunity, including immune enhancement or suppression, we investigated proliferative responses and phenotypes of spleen cells. In addition, kinetics of IFN-${\gamma}$, a Th1 cytokine, was examined in BALB/c mice up to day 6 post-infection (PI). Intraperitoneal injection of mice with $10^3$ KI-1 tachyzoites induced significant decreases (P < 0.05) in proliferative responses of spleen cells. This occurred at days 2-6 PI even when concanavalin A (con A) was added and when stimulated with KI-1 antigen, suggesting suppression of the immunity. $CD4^+$ T-cells decreased markedly at day 2 PI (P < 0.05), whereas $CD8^+$ T-cells, NK cells, and macrophages did not show significant changes, except a slight, but significant, increase of $CD8^+$ T-cells at day 6 PI. The capacity of splenocytes to produce IFN-${\gamma}$ by con A stimulation dropped significantly at days 2-6 PI. These results demonstrate that intraperitoneal injection of KI-1 tachyzoites can induce immunosuppression during the early stage of infection, as revealed by the decrease of $CD4^+$ T-cells and IFN-${\gamma}$.

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References

  1. 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.
  2. Bhopale GM. Pathogenesis of toxoplasmosis. Comp Immunol Microbiol Infect Dis 2003; 26: 213-222. https://doi.org/10.1016/S0147-9571(02)00058-9
  3. Denkers EY, Gazzinelli RT. Regulation and function of T-cellmediated immunity during Toxoplasma gondii infection. Clin Microbiol Rev 1998; 11: 569-588.
  4. Jones JL, Kruszon-Moran D, Wilson M. Toxoplasma gondii infection in the United States, 1999-2000. Emerg Infect Dis 2003; 9: 1371-1374.
  5. Choi WY, Nam HW, Youn JH, Kim WS, Kim WK. Toxoplasma antibody titers by indirect latex agglutination test in patients of Kangnam St. Mary's Hospital and Cheju Medical Center. Korean J ParasitoI 1989;27: 171-175. https://doi.org/10.3347/kjp.1989.27.3.171
  6. Choi WY, Nam HW, Kwak NH, Huh W, Kim YR, Kang MW, Cho SY, Dubey JP. Foodbome outbreaks of human toxoplasmosis. J Infect Dis 1997; 175: 1280-1282. https://doi.org/10.1086/593702
  7. Chai JY, Lin A, Shin EH, Oh MD, Han ET, Nam HW, Lee SH. Laboratory passage and characterization of an isolate of Toxoplasma gondii from an ocular patient in Korea. Korean J Parasitol 2003; 41: 147-154. https://doi.org/10.3347/kjp.2003.41.3.147
  8. Lin A, Shin EH, Kim TY, Park JH, Guk SM, Chai JY. Genetic characteristics of the Korean isolate KI-1 of Toxoplasma gondii. Korean J Parasitol 2005; 43: 27-32. https://doi.org/10.3347/kjp.2005.43.1.27
  9. Gazzinelli R, Xu Y, Hieny S, Cheever A, Sher A. Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii. J Immunol 1992; 149: 175-180.
  10. Denkers EY. From cells to signaling cascades: manipulation of innate immunity by Toxoplasma gondii. FEMS Immunol Med Microbiol 2003; 39: 193-203. https://doi.org/10.1016/S0928-8244(03)00279-7
  11. Suzuki Y, Orellana MA, Schreiber RD, Remington JS. Interferon-$\gamma$: the major mediator of resistance against Toxoplasma gondii. Science 1988; 240: 516-518. https://doi.org/10.1126/science.3128869
  12. Suzuki Y, Conley FK, Remington JS. Importance of endogenous IFN-$\gamma$ for prevention of toxoplasmic encephalitis in mice. J Immunol 1989; 143: 2045-2050:
  13. Shin EH, Kim SB, Nam HW, Han ET, Park JH, Ahn HJ, Chai JY. Use of monoclonal antibodies for flow cytometric detection of intracellular Toxoplasma gondii in murine splenic lymphocytes. J ParasitoI 2004;90: 161-166. https://doi.org/10.1645/GE-3183
  14. Channon JY, Suh EI, Seguin RM, Kasper LH. Attachment ligands of viable Toxoplasma gondii induce soluble immunosuppressive factors in human monocytes. Infect Immun 1999; 67: 2547-2551.
  15. Wei S, Marches J, Borvak J, Zou W, Channon J, White M, Radke J, Cesbron-Dclauw MF, Curiel TJ. Toxoplasma gondii-infected human myeloid dendritic cells induce T-Iymphocyte dysfunction and contact-dependent apoptosis. Infect Immun 2002; 70: 1750- 1760. https://doi.org/10.1128/IAI.70.4.1750-1760.2002
  16. Lee EJ, Heo YM, Choi JH, Song HO, Ryu JS, Ahn MH. Suppressed production of pro-inflammatory cytokines by LPS-activated macrophages after treatment with Toxoplasma gondii lysate. Korean J Parasitol 2008; 46: 145-151. https://doi.org/10.3347/kjp.2008.46.3.145
  17. Kankova S, Holan V, Zajicova A, Kodym P, Flegr J. Modulation of immunity in mice with latent toxoplasmosis-the experimental support for the immunosuppression hypothesis of Toxoplasmainduced changes in reproduction of mice and humans. Parasitol Res 2010; 107: 1421-1427. https://doi.org/10.1007/s00436-010-2013-9
  18. Buzoni-Gatel D, Werts C. Toxoplasma gondii and subversion of the immune system. Trends Parasitol 2006; 22: 448-452. https://doi.org/10.1016/j.pt.2006.08.002
  19. Shin EH, Chai JY. 2007. T-helper-1 and T-helper-2 immune responses in mice infected with the intestinal fluke Neodiplostomum seoulense: their possible roles in worm expulsion and host fatality. J Parasitol 2007; 93: 1036-1045. https://doi.org/10.1645/GE-1203R.1
  20. Choi WY, Nam HW, Youn JH, Kim DJ, Kong Y, Kang SY, Cho SY. Detection of antibodies in serum and cerebrospinal fluid to Toxoplasma gondii by indirect latex. agglutination test and enzymelinked immunosorbent assay. Korean J Parasitol 1992; 30: 83-90. https://doi.org/10.3347/kjp.1992.30.2.83
  21. Casciotti L, Ely KH, Williams ME, Khan IA. CD8+ T-cell immunity against Toxoplasma gondii can be induced but not maintained in mice lacking conventional CD4+ T cells. Infect Immun 2002; 70: 434-443. https://doi.org/10.1128/IAI.70.2.434-443.2002
  22. Guiton R, Zagani R, Dimier-Poisson I. Major role for CD8+ T cells in the protection against Toxoplasma gondii following dendritic cell vaccination. Parasite Immunol 2009; 31: 631-640. https://doi.org/10.1111/j.1365-3024.2009.01146.x
  23. Scharton-Kersten TM, Wynn TA, Denkers EY, Bala S, Showe L, Grunvald E, Hieny S, Gazzinelli RT, Sher A. In the absence of endogenous IFN-$\gamma$, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection. J Immunol 1996; 157: 4045-4054.
  24. Charles E, Joshi S, Ash JD, Fox BA, Farris D, Bzik DJ, Lang ML, Blader JJ. CD4 T-cell suppression by cells from Toxoplasma gondiiinfected retinas is mediated by surface protein PD-L1. Infect Immun 2010; 78: 3484-3492. https://doi.org/10.1128/IAI.00117-10