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Temperature-sensitive mutants of Toxoplasma gondii: pathogenicity and persistence in mice
Abstract:
Certain temperature-sensitive mutants of the RH strain of Toxoplasma gondii and a "back mutant," all maintained in human fibroblasts, were studied in mice. Most mutants gave rise to acute, fatal infections, and after sulfonamide prophylaxis rarely persisted as chronic infections in mice. However, the ts-4 strain was nonfatal in doses up to 10(3) to 10(5) tachyzoites, elicited high titers of antibody, and did not persist beyond 2 mo. No Toxoplasma cysts were found. There was no evidence that a febrile reaction of the mice was restrictive, because the highest temperatures, 37.9 to 38.4 C, occurred 3 days after infection, whereas the organisms were recoverable for 16 to 32 days. Because doses of Toxoplasma, survived by 11 of 12 normal BALB/c mice, and by one of five thymic transplanted athymic mice, killed six of six athymic mice, it appears that the limited persistence of ts-4 is related to the immunologic response.
Insights
The temperature-sensitive ts-4 mutant of Toxoplasma gondii caused non-fatal infections in mice, inducing antibodies but limited persistence. This limited persistence appears linked to the host's immune response.
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- Toxoplasma gondii is an opportunistic parasite.
- Temperature-sensitive mutants offer insights into parasite-host interactions.
Purpose of the Study:
- To investigate the infectivity and persistence of a temperature-sensitive Toxoplasma gondii mutant (ts-4) in a mouse model.
- To explore the role of the host immune system in controlling ts-4 infections.
Main Methods:
- Infection of BALB/c mice and athymic mice with varying doses of ts-4 tachyzoites.
- Monitoring of infection course, antibody titers, and parasite persistence.
- Assessment of host febrile response and its impact on parasite survival.
Main Results:
- The ts-4 strain was non-fatal at doses up to 10(5) tachyzoites and did not persist beyond 2 months.
- Infection elicited high antibody titers but did not lead to cyst formation.
- Athymic mice showed significantly higher susceptibility to ts-4 infection compared to normal mice, suggesting immune involvement.
Conclusions:
- The limited persistence of the ts-4 mutant in immunocompetent mice is likely due to the host's immunologic response.
- The ts-4 mutant serves as a valuable tool for studying T. gondii-host interactions and immune evasion strategies.