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Exp Parasitol. 1996 Nov;84(2):102-14.

Toxoplasma gondii: evidence for interleukin-12-dependent and-independent pathways of interferon-gamma production induced by an attenuated parasite strain.

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Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA.


Immunity in mice infected with Toxoplasma gondii is dependent upon the ability to generate protective levels of the cytokine IFN-gamma. In this report, we present evidence that the attenuated vaccine strain, ts-4, induces the latter cytokine by both IL-12-dependent and -independent pathways. In contrast, strain ME49 appears to induce IFN-gamma wholly in dependence upon IL-12. Thus, 88% of wildtype C57BL/6 mice treated with anti-IL-12 mAb survive ts-4 infection, unlike similarly treated ME49-infected animals. Moreover, while anti-IL-12 treatment reduced early IFN-gamma and nitric oxide production to background levels in ts-4-infected scid animals, the same treatment in infected C57BL/6 mice had no effect on production of the latter mediators. In addition, we found that anti-IL-12 treatment induces 100% mortality in CD(4+)-deficient MHC class II knockout mice infected with ts-4. Finally, production of nitric oxide (a molecule implicated in parasite control) was abrogated in ts-4-infected scid mice following depletion of IFN-gamma producing NK cells. Together, our results suggest that ts-4 induces IL-12-dependent and -independent IFN-gamma production in normal mice, but ME49 induces the latter cytokine only in dependence upon IL-12. Our data, furthermore, implicate involvement of T cells in the IL-12-independent component of the IFN-gamma response.

[Indexed for MEDLINE]

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