The live attenuated DGAT1-knockout whole-cell Toxoplasma vaccine confers protective immunity against acute and chronic toxoplasmosis
The intravacuolar parasite Toxoplasma gondii scavenges fatty acids from host mammalian cells and stores excess in lipid droplets. To investigate the physiological relevance of neutral lipid storage in Toxoplasma, we generated a mutant lacking DGAT1, an ER-localized enzyme that synthesizes triacylglycerols, from the virulent type I RH strain of T. gondii. Compared to WT, RH {triangleup}DGAT1…
Toxoplasma gondii, a parasite that preys on mammalian cells and stores excess fatty acids in lipid droplets, was the subject of a study. Researchers created a mutant strain of T. gondii lacking DGAT1, an enzyme responsible for synthesizing triacylglycerols in the ER. This DGAT1-knockout parasite exhibited poor growth in mammalian cells, formed fewer lipid droplets, experienced lipotoxicity, and did not cause disease or death in mice, both immunocompetent and immunodeficient.
However, mice that were immunized with the DGAT1-knockout parasite developed robust immune responses, including high levels of T. gondii-specific IgG antibodies, effector memory T cells, and a balanced Th1/Th2 response characterized by pro-inflammatory and anti-inflammatory cytokines. This immunity was found to offer complete and long-lasting protection (up to 6 months) against both rechallenge with homologous type I (acute infection) and heterologous cyst-forming type II (chronic infection) strains of T. gondii.
Further investigation showed that IFN-gamma, CD8+ T cells, and B cells were essential for defending against type I T. gondii in immunized mice. Consequently, the live-attenuated RH DGAT1 strain emerged as a promising vaccine candidate and a valuable model for studying immune responses that combat T. gondii infections.
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