Toxoplasma TgCtwh3 Δrop16 (â /â ¢) accelerates neuronal apoptosis and APP production in mouse with acute infection.

OBJECTIVE: To explore the mechanism by which rop16 (â /â ¢) -deficient/gra15 (â ¡) -dominant toxoplasma gondii Chinese 1 genotype Wh3 (TgCtwh3 Δrop16 (â /â ¢) ) strain induced neuron apoptosis, APP and BACE1 production in vivo and vitro. METHOD: BALB/c mice were infected by intraperitoneal injection with TgCtwh3 wild type (TgCtwh3 WT) and TgCtwh3 Δrop16 (â /â ¢) tachyzoites, respectively. One week after infection, the morphology and number of hippocampal neurons were examined by hematoxylin-eosin (H&E) and Nissl staining. Expression levels of apoptosis-related proteins, APP, BACE1 as well as inflammatory factors proteins and genes in the hippocampus were evaluated using western blotting and qRT-PCR. The hippocampal neuron cell line HT22 was infected with TgCtwh3 WT and TgCtwh3 Δrop16 (â /â ¢) tachyzoite, respectively, and the expression of target proteins was analyzed through immunofluorescence staining and western blotting. Furthermore, HT22 apoptosis was assessed using flow cytometry. RESULT: BALB/c mice injected with TgCtwh3 Δrop16 (â /â ¢) tachyzoites presented abnormal appearance and posture changes as well as declined vitality. The hippocampus assay demonstrated that TgCtwh3 Δrop16 (â /â ¢) toxoplasma caused neuron loss, neuron alignment disorder, neuronal nucleus abnormal deep-stained and neuron apoptosis. Furthermore, TgCtwh3 Δrop16 (â /â ¢) tachyzoites caused obvious production of APP, BACE1and expression increase of pro-inflammatory factors in hippocampal tissue compared to these in mice infected with TgCtwh3 WT tachyzoites. Contrarily, the expression of transforming growth factor beta 1 (TGF-β1), a pivotal anti-inflammatory cytokine was significantly decreased in TgCtwh3 Δrop16 (â /â ¢) infected mice. Further study showed that TgCtwh3 Δrop16 (â /â ¢) tachyzoites induced HT22 apoptosis through triggering ERS, meanwhile promoted HT22 to produce APP, BACE1 by activating NF-κB signaling pathway. CONCLUSION: Our results indicated that the GRA15(â ¡) effector may play a crucial part in neuron apoptosis, pro-inflammatory factors secretion, and APP, BACE1 production. Inversely, ROP16(â /â ¢) effector may play a potentially protective role in this process.