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.
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.
Hiramoto
Roberto Mitsuyoshi
RM
Molecular Biology Laboratory, Instituto de Pesquisas Energéticas e Nucleares-IPEN, Travessa R, 400, Cidade Universitária, 05508-900 São Paulo, SP, Brazil.
Galisteo
Andrés Jimenez
AJ
do Nascimento
Nanci
N
de Andrade
Heitor Franco
HF
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004249:DNA Damage; D005720:Gamma Rays; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016052:Protozoan Vaccines / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D014123:Toxoplasmosis / Q000276:immunology*
D016207:Cytokines; D016052:Protozoan Vaccines