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 pa tient) of Toxoplasma gondii could induce cross-protection in mice against i nfection with a lethal dose of the PLK strain. Mice were first infected wit h tachyzoites (5 x 10(5)) of PTN and 5 days later challenged with PLK (1 X 10(5), 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 in fection alone died between 5 and 11 days after infection. The protection wa s accompanied by an increased expansion of NK cells and CD4+ T cells. This condition was associated by increased production of IFN-gamma and an augmen ted number of IFN-gamma-producing cells in the spleen. Further, PTN + PLK-i nfected mice showed higher production of TNF-alpha and nitrite compared to PLK-infected mice. Mice infected with the PTN strain had an enhanced capaci ty to activate the immune system early in infection since they produced hig her levels of IFN-gamma, TNF-alpha, and NO than PLK-infected mice. Administ ration of anti-IFN-gamma mAb or anti-asialo GM1 antibody resulted in 100 an d 20% mortality respectively, in PTN-infected mice but no death in PTN + PL K-infected mice. Together, these results suggest that early production of I FN-gamma and NK-cell activity is important in protection against PTN infect ion, whereas in PTN + PLK infection components of adaptive immunity rapidly developed following elaboration of an effective early innate immune respon se. (C) 1999 Academic Press.