Infection of mouse neural progenitor cells by Toxoplasma gondii affects in vitro proliferation, differentiation and migration
2021
Congenital toxoplasmosis constitutes a major cause of pre- and post-natal
complications. Fetal infection with Toxoplasma gondii influences development and can
lead to microcephaly, encephalitis, and neurological abnormalities. Few studies have attempted to explain the impact of T. gondii infection on the physiology of mature nerve
cells, and no systematic study concerning the effect of infection of neural progenitor cells
by T. gondii in the biology of these progenitors is available. We infected cortical intermediate progenitor cell cultivated as neurospheres obtained from E16.5 Swiss
Webster mice with T. gondii (Me49 strain) tachyzoites to mimic the developing mouse
cerebral cortex in vitro. Infection decreased cell proliferation as detected by Ki67 staining
at 48 and 72 hours post infection (hpi) in floating neurospheres, resulting in reduced
cellularity at 96 hpi. Neurogenic and gliogenic potential, assessed in plated
neurospheres, was shown to be impaired in infected cultures, as indicated by
neurofilament heavy chain (NF-200) and GFAP staining, respectively. To further
investigate the impact of infection on neuronal differentiation, Neuro2a neuroblasts were
infected and after 24 hpi, neurogenic differentiation was induced with serum withdrawal.
We confirmed that infection induces a decrease in neuroblast-neuron differentiation rates in cells stained for NF-200, with reduced neuritogenesis. Migration rates were analyzed
in plated neurospheres. At 120 h after plating, infected cultures exhibited decreased
overall migration rates and altered the radial migration of nestin-, GFAP- and NF-200-
positive cells. These findings indicate that T. gondii infection of neural progenitor cells
may lead to reduced neuro/gliogenesis due to an imbalance in cell proliferation alongside
an altered migratory profile. If translated to the in vivo situation, these data could explain,
in part, the cortical malformations observed in congenitally infected individuals.
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