AUTHOR=Jin Yu , Yao Yong , El-Ashram Saeed , Tian Jiaming , Shen Jilong , Ji Yongsheng 

TITLE=The Neurotropic Parasite Toxoplasma gondii Induces Astrocyte Polarization Through NFκB Pathway

JOURNAL=Frontiers in Medicine

VOLUME=6

YEAR=2019

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2019.00267

DOI=10.3389/fmed.2019.00267

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold><italic>Toxoplasma gondii</italic> is a protozoan parasite that chronically infects nearly one-third of the world's human population. In immunosuppressed individuals and fetus, infection with <italic>T. gondii</italic> contributes to a series of devastating conditions, including toxoplasmic encephalitis (TE), which is characterized by neuron damage in the central nervous system (CNS). Astrocyte polarization is currently found in some neurodegenerative diseases, and A1 subtype of astrocyte leads to neuron apoptosis. However, little information has been available on the role of astrocyte polarization in TE.</p><p><bold>Methods:</bold> In the present study, we established a mouse model to study TE and detected A1 astrocyte in the brains of mice with TE. Expression level of A1 astrocyte-specific marker C3 was evaluated using indirect fluorescent assay (IFA) and Western blotting. Primary mouse astrocytes were incubated with different concentrations of <italic>T. gondii</italic> excreted-secreted antigens (<italic>Tg</italic>ESAs) <italic>in vitro</italic>. Expression level of C3 and A1 astrocyte-specific transcription levels were assessed using Western blotting and qRT-PCR, respectively. Bay11-7082 was used to study nuclear factor (NF) κB pathway in <italic>Tg</italic>ESA-induced astrocyte polarization.</p><p><bold>Results:</bold> In mice with TE, the proportion of A1 astrocyte (GFAP<sup>+</sup>C3<sup>+</sup>) increased significantly. The results of <italic>in vitro</italic> study showed that <italic>Tg</italic>ESAs induced astrocyte polarization to A1 subtype. Blocking of NFκB pathway by Bay11-7082 inhibited <italic>Tg</italic>ESA-induced astrocyte polarization.</p><p><bold>Conclusions:</bold> Our preliminary study showed the involvement of A1 astrocyte in the process of TE in mice, and <italic>Tg</italic>ESAs could trigger astrocyte to polarize to A1 subtype. These findings suggest a new mechanism underlying the neuropathogenesis induced by <italic>T. gondii</italic> infection.</p>