Abstract
Background: Toxoplasma gondii is a protozoan parasite that chronically infects nearly one-third of the world's human population. In immunosuppressed individuals and fetus, infection with T. gondii 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.Methods: 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 T. gondii excreted-secreted antigens (TgESAs) in vitro. 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 TgESA-induced astrocyte polarization.Results: In mice with TE, the proportion of A1 astrocyte (GFAP+C3+) increased significantly. The results of in vitro study showed that TgESAs induced astrocyte polarization to A1 subtype. Blocking of NFκB pathway by Bay11-7082 inhibited TgESA-induced astrocyte polarization.Conclusions: Our preliminary study showed the involvement of A1 astrocyte in the process of TE in mice, and TgESAs could trigger astrocyte to polarize to A1 subtype. These findings suggest a new mechanism underlying the neuropathogenesis induced by T. gondii infection.
Highlights
Toxoplasma gondii is an obligate intracellular protozoan parasite that chronically infects the central nervous system (CNS) of up to one-third of the human population in the world [1]
We aimed to investigate the effects of the excreted-secreted antigens (ESAs) of T. gondii (Tg-ESAs) on astrocyte polarization and assess the involvement of nuclear factor (NF) κB signaling pathway in Tg-ESAs-induced astrocyte polarization
Six weeks later, Toxoplasmainfected mice were immunosuppressed by intraperitoneal injection with cyclophosphamide to reactivate chronic T. gondii infection
Summary
Toxoplasma gondii is an obligate intracellular protozoan parasite that chronically infects the central nervous system (CNS) of up to one-third of the human population in the world [1]. Upon infection with T. gondii, fast-replicating tachyzoites infect a wide range of host cells, including neurons. In TE, T. gondii bradyzoites within cysts switch to tachyzoites, which infect and destroy brain-resident cells. Toxoplasma gondii is a protozoan parasite that chronically infects nearly one-third of the world’s human population. In immunosuppressed individuals and fetus, infection with T. gondii contributes to a series of devastating conditions, including toxoplasmic encephalitis (TE), which is characterized by neuron damage in the central nervous system (CNS). Little information has been available on the role of astrocyte polarization in TE
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