Protection against lethal toxoplasmosis in mice by an avirulent strain of Toxoplasma gondii: stimulation of IFN-gamma and TNF-alpha response.
In this study, we examined whether the PTN strain (isolated from an AIDS patient) of Toxoplasma gondii could induce cross-protection in mice against infection with a lethal dose of the PLK strain. Mice were first infected with tachyzoites (5 x 10(5)) of PTN and 5 days later challenged with PLK (1 x 10(5), LD(90)) parasites. None of these mice succumbed to infection until day 21 after infection, whereas 100% of the mice given the same dose of PLK infection alone died between 5 and 11 days after infection. The protection was accompanied by an increased expansion of NK cells and CD4 + T cells. This condition was associated by increased production of IFN-gamma and an augmented number of IFN-gamma-producing cells in the spleen. Further, PTN + PLK-infected mice showed higher production of TNF-alpha and nitrite compared to PLK-infected mice. Mice infected with the PTN strain had an enhanced capacity to activate the immune system early in infection since they produced higher levels of IFN-gamma, TNF-alpha, and NO than PLK-infected mice. Administration of anti-IFN-gamma mAb or anti-asialo GM1 antibody resulted in 100 and 20% mortality, respectively, in PTN-infected mice but no death in PTN + PLK-infected mice. Together, these results suggest that early production of IFN-gamma and NK-cell activity is important in protection against PTN infection, whereas in PTN + PLK infection components of adaptive immunity rapidly developed following elaboration of an effective early innate immune response.
Haque
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Department of Medicine and Microbiology, Dartmouth Medical School Hanover, New Hampshire, 03755, USA. s.haque@medecine.univ-mrs.fr
Franck
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Dumon
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Kasper
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LH
Haque
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D007106:Immune Sera / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014774:Virulence
D000911:Antibodies, Monoclonal; D007106:Immune Sera; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005677:G(M1) Ganglioside; D007371:Interferon-gamma