Toxoplasma gondii: evidence for interleukin-12-dependent and-independent pathways of interferon-gamma production induced by an attenuated parasite strain.
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.
Scharton-Kersten
T
T
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA.
Caspar
P
P
Sher
A
A
Denkers
E Y
EY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009569:Nitric Oxide / Q000096:biosynthesis; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology; D014774:Virulence
D000911:Antibodies, Monoclonal; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma