Toxoplasma gondii type II Pru and its derivative Pru∆KU80 : investigation of similarities and differences -

Abstract

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular parasite. The host-induced immune response to the infection dictates the ability of this parasite to switch from the acute (tachyzoite stages) to the chronic phase (bradyzoite stages) of infection, where it encysts in the brain under the tight control of the host immune system. The immune response against T. gondii is IFN-ɣ driven where the parasite control occurs via the production of iNOS which distates whether these parasites are cleared at the level of the peritoneum or the brain. PruΔKU80 has not been studied in comparison to its parental Pru strain and it is of importance to know whether these two type II strains exhibit the same properties at the level of cysts induction in the brain and immune response. We have compared the transcription levels of BAG-1 during chronic infection to decide which mouse strain is the best murine model for parasite induction by Pru and PruΔKU80 strains. Then we tested the differences in the capacity of these parasites to replicate inside macrophages during the acute and chronic stages of the infection by comparing SAG-1 transcription levels. We finally studied the immune response by these type II parasites in the mouse model of choice during acute and chronic infection through the comparison of IFN-ɣ, iNOS and IL-10 transcription levels as well as IL-12 secreted levels. We found that among the three mouse strains (Swiss Webster, Balb-c and Black-6), Swiss Webster mice showed the highest amounts of cysts when infected with Pru strain that caused stronger expression levels of BAG-1 compared to the Pru∆KU80 strain. We investigated the immune response in the brain of chronically infected mice and showed that no significant difference in IFN-ɣ and iNOS levels was observed in either Pru or Pru∆KU80 infected mice. Further investigation showed that the Pru parasites escape the peritoneum and organs to reach the brain where they encyst where as Pru[u220