Yongli Zhang, Wei Hu, Qiang Liu, Zelin Ma, Shouping Hu, Zhuo Zhang, HongLin Jia, Xijun He

Exp Mol Pathol.2021 Sep 18;104684.doi: 10.1016/j.yexmp.2021.104684. Online ahead of print.

Abstract

The immunoproteasomes are specific proteasomes that clear oxidant-damaged proteins under inflammatory conditions in various diseases. Toxoplasma gondii (T. gondii) infects the central nervous system, causing encephalitis. However, the relationship between the immunoproteasomes and brain inflammation during T. gondii infection is not well characterized. In this study, we established an in vivo mouse model of T. gondii PLK strain infection via intraperitoneal injection and evaluated the expression of immunoproteasome subunits in the brains of infected mice. The results demonstrated that first, pathological changes in the brains of infected mice increase in severity over time. Second, following T. gondii infection, activated microglia and astrocytes undergo a series of functional alterations and morphological transformations, including proliferation and migration. Third, T. gondii infection induces expression of inflammatory cytokines, including IFN-γ, IL-1β, TNF-α, and IL-6. Fourth, the immunoproteasome subunits low-molecular-weight polypeptide 2 (LMP2), LMP7, and LMP10 mRNA and protein levels are significantly upregulated in T. gondii-infected mouse brains, as shown by the RT-qPCR and western blot analysis, compared with that in vehicle-treated brains, and their expression is localized to the microglia, astrocytes, and neurons of T. gondii-infected brains, as determined via immunofluorescence staining. Furthermore, the western blot mean gray value for the immunoproteasome subunits and the positive microglia and astrocyte immunohistochemical signals in the brains of T. gondii-infected mice were positively correlated, indicating that the observed relationships were highly significant. Therefore, it was concluded that the induction of the immunoproteasomes is a pathogenic mechanism underlying T. gondii infection-induced inflammation.

Keywords: Immunoproteasome; Low-molecular-weight polypeptide 10; Low-molecular-weight polypeptide 2; Low-molecular-weight polypeptide 7; Mice; Toxoplasma gondii.

Copyright © 2018. Published by Elsevier Inc.