Protection against Lethal Toxoplasmosis in Mice by an Avirulent Strain of Toxoplasma gondii: Stimulation of IFN-γ and TNF-α Response

• Published in: Experimental parasitology 1999-12, Vol.93 (4), p.231-240
• Main Authors: Haque, Sakhina, Franck, Jacqueline, Dumon, Henri, Kasper, Lloyd H., Haque, Azizul
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Antibodies, Monoclonal - immunology; Biological and medical sciences; Experimental protozoal diseases and models; Female; G(M1) Ganglioside - immunology; g-Interferon; IFN-γ, TNF-α; Immune Sera - immunology; Immunophenotyping; Infectious diseases; innate immunity; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Killer Cells, Natural - immunology; Medical sciences; Mice; Mice, Inbred CBA; Nitric Oxide - biosynthesis; NK-cells; parasite isolate; Parasitic diseases; protection; Protozoal diseases; Spleen - cytology; T-Lymphocytes - classification; T-Lymphocytes - immunology; Toxoplasma - immunology; Toxoplasma - pathogenicity; Toxoplasma gondii; Toxoplasmosis, Animal - immunology; Toxoplasmosis, Animal - mortality; Toxoplasmosis, Animal - prevention & control; tumor necrosis factor-^a; Tumor Necrosis Factor-alpha - biosynthesis; Virulence
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1006/expr.1999.4457

Haque, S., Franck, J., Dumon, H., Kasper, L. H., and Haque, A. 1999. Protection against lethal toxoplasmosis in mice by an avirulent strain of Toxoplasma gondii: Stimulation of IFN-γ and TNF-α response. Experimental Parasitology93, 231–240. 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 × 105) of PTN and 5 days later challenged with PLK (1 × 105, LD90) 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-γ and an augmented number of IFN-γ-producing cells in the spleen. Further, PTN + PLK-infected mice showed higher production of TNF-α 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-γ, TNF-α, and NO than PLK-infected mice. Administration of anti-IFN-γ 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-γ 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.