Immunization with heat-killed Toxoplasma gondii stimulates an early IFN-gamma response and induces protection against virulent murine malaria.
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.
Haque
A
A
Immunologie et Génétique des Maladies Parasitaires, INSERM U399, Faculté de Medecine, La Timone, Marseille, France. haque@club-internet.fr
Graille
M
M
Kasper
L H
LH
Haque
S
S
D000818:Animals; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008288:Malaria / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D010967:Plasmodium yoelii / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D014122:Toxoplasma / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015164:Vaccines, Inactivated / Q000276:immunology
D016052:Protozoan Vaccines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015164:Vaccines, Inactivated; D009569:Nitric Oxide; D007371:Interferon-gamma