ROP9, MIC3, and SAG2 are heparin-binding proteins in Toxoplasma gondii and involved in host cell attachment and invasion

Acta Trop. 2019 Apr:192:22-29. doi: 10.1016/j.actatropica.2019.01.001. Epub 2019 Jan 18.

Abstract

Toxoplasma gondii (T. gondii) is an obligatory intracellular parasite that can infect varieties of warm-blooded animals, including humans and birds. Heparan sulfate (HS) is widely distributed on the eukaryotic cell surface of vertebrates and can inhibit T. gondii invasion. In this study, we investigated the transcription and expression of the level of TgROP9, TgMIC3, and TgSAG2 in T. gondii RH strain, and found that the expression levels of these three proteins in invading parasites were higher compared to those free ranging parasites. The recombinant proteins showed specific binding activity to both heparin and host cell surface. Incubation of these proteins with the host cells could block T. gondiiinvasion. Furthermore, protein-specific antibodies also blocked parasite invasion. Antibodies in the sera of T. gondii infected individuals recognized the recombinant TgROP9, TgMIC3, and TgSAG2, which suggested the exposure of these proteins to human immune system. Mice immunized with the three proteins exhibited protective immunity against lethal challenge. The data collectively suggested that these parasitic proteins may be used as candidate antigens for development of anti-toxoplasmosis vaccine.

Keywords: Adherence; Heparin-binding; Invasion; MIC3; ROP9; SAG2; Toxoplasma gondii; Vaccine candidates.

MeSH terms

  • Animals
  • Antibodies, Protozoan
  • Antigens, Protozoan / pharmacology*
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Carrier Proteins
  • Female
  • Heparitin Sulfate / immunology*
  • Immunization / methods*
  • Membrane Glycoproteins / pharmacology
  • Membrane Proteins / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins / pharmacology
  • Protozoan Vaccines / pharmacology*
  • Recombinant Proteins
  • Toxoplasma / immunology*
  • Vaccines, DNA

Substances

  • AZU1 protein, human
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Carrier Proteins
  • MIC3 protein, Toxoplasma gondii
  • Membrane Glycoproteins
  • Membrane Proteins
  • Protozoan Proteins
  • Protozoan Vaccines
  • ROP9 protein, Toxoplasma gondii
  • Recombinant Proteins
  • SAG3 protein, Toxoplasma gondii
  • Vaccines, DNA
  • Heparitin Sulfate