Toxoplasma gondii inhibits differentiation of C17.2 neural stem cells through Wnt/β-catenin signaling pathway

Radial Glia cell infection byToxoplasma gondiidisrupts brain microvascular endothelial cell integrity

“…On the other hand, a reduction in β-III-tubulin positive cell numbers was detected, without affecting apoptotic neuronal population, suggesting inhibition of neurogenesis. This finding is corroborated by the recent demonstration that T. gondii infection impairs neuron generation from C17.2 neural stem cell line in vitro (Gan et al, 2016; Zhang et al, 2017). However, it is possible that, in addition to T. gondii induced alterations of well-known molecular mechanisms that control neurogenesis during cortical development, such as Wnt/βcat signaling (Gan et al, 2016; Zhang et al, 2017) and neuronal differentiation transcription factors, such as Fabp7/BLBP, Sox2, Tacc3 Eya1, Sox2, and Tnfrsf12a genes (Xiao et al, 2012), altered levels of IL-6, TGF-β1 and other, still unidentified cytokines, might exert an autocrine effect on the neurogenic potential of RG cells.…”

“…This finding is corroborated by the recent demonstration that T. gondii infection impairs neuron generation from C17.2 neural stem cell line in vitro (Gan et al, 2016; Zhang et al, 2017). However, it is possible that, in addition to T. gondii induced alterations of well-known molecular mechanisms that control neurogenesis during cortical development, such as Wnt/βcat signaling (Gan et al, 2016; Zhang et al, 2017) and neuronal differentiation transcription factors, such as Fabp7/BLBP, Sox2, Tacc3 Eya1, Sox2, and Tnfrsf12a genes (Xiao et al, 2012), altered levels of IL-6, TGF-β1 and other, still unidentified cytokines, might exert an autocrine effect on the neurogenic potential of RG cells. Although T. gondii infection decreased the number of Nestin/BLBP and β-III-tubulin positive cells and did not alter GFAP cells numbers, overall cell composition percentages induced an increase in an unidentified cell population, suggesting that RG differentiation might favor the appearance of other cell types.…”

“…Evidence suggest that neural progenitors are directly affected by the TORCH complex of perinatal infectious diseases that, ultimately, lead to malformations in the cerebral cortex, such as microcephaly, mostly by disrupting neural cells generation (Neu et al, 2015). Regarding infection with T. gondii , recent findings point to increased apoptosis and reduced cell differentiation in the C17.2 neural stem cell line (Gan et al, 2016; Wang et al, 2014; Zhang et al, 2017). However, further characterization and evaluation of the effects of T. gondii infection on primary RG cells isolated from embryonic cerebral cortex have not yet been addressed.…”

“…Deleterious effects of infection of mouse neural progenitor cells by a highly infective T. gondii strain was linked to apoptosis induction by endoplasmic reticulum stress signaling pathway activation (Wang et al, 2014). In addition, reduced neuron and astrocyte generation from the neural C17.2 stem cell line by disruption of the Wnt/β–catenin signaling pathway have also been suggested as an underlying mechanism of T. gondii -induced neural pathological damage during brain development (Gan et al, 2016; Zhang et al, 2017).…”

A mechanistic study of Toxoplasma gondii ROP18 inhibiting differentiation of C17.2 neural stem cells

“…These findings may partly explain the possible mechanisms of pathological brain damage caused by congenital T. gondii infection [ 18 , 19 ]. Furthermore, we recently found that the excreted-secreted antigens (ESAs) of T. gondii RH inactivated the differentiation of C17.2 NSCs and downregulated the expression level of β-catenin [ 20 ]. β-catenin is a crucial component of the Wnt/β-catenin signaling pathway.…”