A Role for Basigin in Toxoplasma gondii Infection

Azadeh Nasuhidehnavi, Yanlin Zhao, Ankita Punetha, Andrew Hemphill, Hong Li, Tyler J. Bechtel, Theresa Rager, Bingcong Xiong, Vasileios I. Petrou, Marc Jan Gubbels, Eranthie Weerapana, George S. Yap

Research output: Contribution to journalArticlepeer-review

Abstract

The role of specific host cell surface receptors during Toxoplasma gondii invasion of host cells is poorly defined. Here, we interrogated the role of the well-known malarial invasion receptor, basigin, in T. gondii infection of astrocytes. We found that primary astrocytes express two members of the BASIGIN (BSG) immunoglobulin family, basigin and embigin, but did not express neuroplastin. Antibody blockade of either basigin or embigin caused a significant reduction of parasite infectivity in astrocytes. The specific role of basigin during T. gondii invasion was further examined using a mouse astrocytic cell line (C8-D30), which exclusively expresses basigin. CRISPR-mediated deletion of basigin in C8-D30 cells resulted in decreased T. gondii infectivity. T. gondii replication and invasion efficiency were not altered by basigin deficiency, but parasite attachment to astrocytes was markedly reduced. We also conducted a proteomic screen to identify T. gondii proteins that interact with basigin. Toxoplasma-encoded cyclophilins, the protein 14-3-3, and protein disulfide isomerase (TgPDI) were among the putative basigin-ligands identified. Recombinant TgPDI produced in E. coli bound to basigin and pretreatment of tachyzoites with a PDI inhibitor decreased parasite attachment to host cells. Finally, mutagenesis of the active site cysteines of TgPDI abolished enzyme binding to basigin. Thus, basigin and its related immunoglobulin family members may represent host receptors that mediate attachment of T. gondii to diverse cell types.

Original languageEnglish (US)
JournalInfection and immunity
Volume90
Issue number8
DOIs
StatePublished - Aug 2022

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Keywords

  • Toxoplasma
  • astrocyte
  • attachment
  • basigin
  • central nervous system infections

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