Toxoplasma gondii prevalent in China induce weaker apoptosis of neural stem cells C17.2 via endoplasmic reticulum stress (ERS) signaling pathways

BACKGROUND: Toxoplasma gondii, an obligate intracellular pathogen, has a strong affinity for the nervous system. TgCtwh3, a representative Chinese 1 Toxoplasma strain prevalent in China, has the polymorphic features of the effectors ROP16(I/III) with type I and GRA15(II) with type II Toxoplasma strains. The interaction of this atypical strain with host cells remains extremely elusive. METHODS: Using a transwell system, neural stem cells C17.2 were co-cultured with the tachyzoites of TgCtwh3 or standard type I RH strain. The apoptosis levels of C17.2 cells and the expression levels of related proteins in the endoplasmic reticulum stress (ERS)-mediated pathway were detected by flow cytometry and Western blotting. RESULTS: The apoptosis level of C17.2 cells co-cultured with TgCtwh3 had a significant increase compared to the negative control group; however, the apoptosis level in the TgCtwh3 group was significantly lower than that in the RH co-culture group. Western blotting analyses reveal that, after the C17.2 cells were co-cultured with TgCtwh3 and RH tachyzoites, the expression levels of caspase-12, CHOP and p-JNK in the cells increased significantly when compared to the control groups. After the pretreatment of Z-ATAD-FMK, an inhibitor of caspase-12, the apoptosis level of the C17.2 cells co-cultured with TgCtwh3 or RH tachyzoites had an apparent decline, and correspondingly, the expression levels of those related proteins were notably decreased. CONCLUSIONS: Our findings suggest that TgCtwh3 may induce the apoptosis of the C17.2 cells by up-regulation of caspase-12, CHOP, and p-JNK, which are associated with ERS signaling pathways. This work contributes to better understanding the possible mechanism of brain pathology induced by T. gondii Chinese 1 isolates prevalent in China, and also reveals the potential value of ERS inhibitors to treat such related diseases in the future.