Immunization With Heat-Killed Toxoplasma Gondii Stimulates an Early IFN-gamma Response and Induces Protection Against Virulent Murine Malaria

Vaccine. 1999 Jun 4;17(20-21):2604-11. doi: 10.1016/s0264-410x(99)00050-x.


In this study, we describe protection of BALB/c mice by immunization with heat-killed T. gondii tachyzoites against infection with Plasmodium yoelii 17XL which causes cerebral malaria and death in mice by day 7-8 post infection. Immunization resulted significant reduction in parasitemia at the peak period of infection. Protection induced by heat-killed T. gondii was associated with marked increase in NK cell number and IFN-gamma mRNA expression early in the infection. The level of IFN-gamma or TNF-alpha was found to diminish in T. gondii-treated mice as the infection progressed to the late stage. This declined response of IFN-gamma or TNF-alpha was associated with marked increase in the expression of IL-10, a counterregulatory cytokine. Pretreatment of mice with live T. gondii induced poor level of protection as compared with that of heat-killed parasites. Mice that received P. yoelii infection alone, had an elevated IFN-gamma response in the late stage of infection. Development of cerebral malaria in untreated mice was accompanied by an augmented production of TNF-alpha and nitric oxide (NO), the proinflammatory mediators. These findings suggest that nonspecific immunization with T. gondii leads to restoration of an early IFN-gamma response in P. yoelii-infected mice and in the establishment of an immunoregulatory mechanism that effectively antagonizes the disease-promoting effects of proinflammatory cytokines in the late phase of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Immunization
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Malaria / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / biosynthesis
  • Plasmodium yoelii / immunology*
  • Protozoan Vaccines / immunology*
  • RNA, Messenger / analysis
  • Toxoplasma / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Vaccines, Inactivated / immunology


  • Protozoan Vaccines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vaccines, Inactivated
  • Nitric Oxide
  • Interferon-gamma