Avirulent Wh6 Strain Of Toxoplasma Gondii Genotype Chinese 1 Induced Complete Protective Immunity Against The Challenge Of High Virulent Wh3 Strain In Mice

Background Toxoplasma gondii is an opportunistic obligate nucleus parasitic protozoa that transmits zoonotic toxoplasmosis in humans and in many animals.There are three types of Toxoplasma gondii virulence,type I,type II and type III,which are dominant in Europe,North America and Africa.The dominant genotype of Toxoplasma gondii in China is Chinese 1 genotype,the most representative of which is the virulent Wh3 strain and the avirulent Wh6 strain.More interestingly,the Wh3 and Wh6 genotypes are up to 90% homologous.The strains all have ROP16I/III and GRA15 II polymorphisms.However,the virulence difference between the two is relatively large,and both strains can polarize macrophages,and the Wh3 strain induces macrophage M2 / Th2 polarization.The Wh6 strain induces macrophage polarization in the M1/Th1 direction.Cellular immunity plays a leading role in anti-toxoplasmosis infection,and is also the most sensitive cell for Toxoplasma infection,and provides an environment for the proliferation of Toxoplasma gondii,which is also an important way of acute infection.Macrophages can produce a variety of biologically active cytokines;they can induce adaptive immune responses to T cells presenting antigens;control and kill parasitics through aerobic and non-oxygen mechanisms.Macrophage play a role in killing intracellular parasites or inhibiting the carrying and spread of the worms,as well as the host’s susceptibility to Toxoplasma gondii,mainly depending on the macrophage activated by the classical pathway(M1)and the function of macrophage activated by the alternative pathway(M2).The shift/polarization of M1 and M2 directly affects the results of innate and acute infections in Toxoplasma infected hosts.Toxoplasma has no effective prevention and treatment drugs,and safe and effective vaccine is one of the strategies to prevent toxoplasmosis.The ideal live insect vaccine can not only stimulate the body to produce effective protection,but also has the no ability to proliferate and spread.Toxoplasma gondii is a foodborne parasitic disease,and most animals are infected by eating food contaminated with cysts.In view of the research on the protective immunity of cross infection of two dominant strains of Chinese dominant genotypes,no report has been reported.Our study used Wh3 and Wh6 strains to establish a BALB/c mouse model of Toxoplasma gondii infection,and explored the immune function of Toxoplasma gondii,providing a theoretical basis for the screening of attenuated live vaccine strains and immune mechanism.Objective The aim of this study was to explore the protective effect of Toxoplasma gondii avirulent Wh6 strain infection on the challenge of the high virulent strain in BALB/cmice,so as to find a new attenuated vaccine of viable parasite.Methods Thirty BALB/c female mice were randomly divided into three groups,Group I,Group II and Group III.BALB/c mice in Group I were intragastrically infected with 25-35 cysts of Wh6 strainwhile mice in Group II,with PBS,and additional 10 mice were used as normal control.At 35 days postinfection,the brain tissues of mice inoculated with avirulent Wh6 strain were examined for Toxoplasma cysts under microscope.Subsequently the mice of Groups I and II were challenged with3000 tachyzoites of high virulent Wh3 strain.One week after challenge,the survival of mice and parasite burden in the peritoneal cavity were evaluated,the suspensions of splenocytes were prepared for detection of Th1 and Th2 cells in the three groups by flow cytometry,q RT-PCR and enzyme-linked immunosorbent assay were used for cytokine measurements.Results All mice in Group I survived for more than 15 days until the experiments ended but the animals in Group II totally died after one week of Wh3 strain infection.The levels of Th1 and Th2 cytokines IFN-γ,IL-10 and IL-12 in the spleen cell culture supernatant of group II were significantly higher than those in group I(p < 0.001).Conclusions: The data indicate that BALB/c mice in oculated with avirulent Wh6 strain may survive the lethal infection of Wh3 strain,suggesting a potential significant role of Wh6 strain in novel approach of viable attenuated parasite vaccine against toxoplasmosis.