200 Gy sterilised Toxoplasma gondii tachyzoites maintain metabolic functions and mammalian cell invasion, eliciting cellular immunity and cytokine response similar to natural infection in mice
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Abstract
200Gy gamma-irradiated Toxoplasma gondii RH tachyzoites failed to reproduce in vitro
and in vivo. In short-term cultures, these parasites maintained a respiratory response,
the ability to invade cells and preserved protein and nucleic acid synthesis. ELISA
and Western blotting techniques demonstrated the similarity in humoral response between
mice infected with gamma-irradiated tachyzoites and animals infected with naive parasites
and treated with sulfadoxine, higher than mice immunised with formaldehyde-killed
tachyzoites. Splenocyte stimulation by T. gondii antigen produced lymphoproliferative
response and cytokine profile (IL-10, IL-12, IFN-gamma and TNF-alpha) similar to those
produced by chronic natural infection. Mice immunised with irradiated tachyzoites
had extended survival times after subsequent tachyzoite challenge, and displayed minimal
cerebral pathology after cyst challenge. Irradiated tachyzoites lose their reproductive
ability whilst maintaining metabolic function and may provide a novel tool for the
study of toxoplasmosis and vaccine development.