Toxoplasma gondii profilin and tachyzoites RH strain may manipulate autophagy via downregulating Atg5 and Atg12 and upregulating Atg7

Mol Biol Rep. 2021 Oct;48(10):7041-7047. doi: 10.1007/s11033-021-06667-5. Epub 2021 Aug 28.

Abstract

Background: Autophagy process is an important defense mechanism against intracellular infection. This process plays a critical role in limiting the development of Toxoplasma gondii. This study aimed to investigate the effects of T. gondii profilin and tachyzoites on the expression of autophagy genes.

Methods and results: PMA-activated THP-1 cell line was incubated with T. gondii profilin and tachyzoites for 6 h. After RNA extraction and cDNA synthesis, the expression of Atg5, Atg7, Atg12, and LC3b was evaluated using real-time PCR. The results revealed statistically significant downregulation of Atg5 for 1.43 (P-value = 0.0062) and 4.15 (P-value = 0.0178) folds after treatment with T. gondii profilin and tachyzoites, respectively. Similar to Atg 5, Atg 12 revealed a statistically significant downregulation for profilin (1.41 fold; P-value = 0.0047) and T. gondii tachyzoites (3.25 fold; P-value = 0.011). The expression of Atg7 elevated in both T. gondii profilin (2.083 fold; P-value = 0.0087) and tachyzoites (1.64 fold; P-value = 0.206). T. gondii profilin and tachyzoites downregulated (1.04 fold; P-value = 0.0028) and upregulated (twofold; P-value = 0.091) the expression of LC3b, respectively.

Conclusions: Our findings suggest that T. gondii and profilin may manipulate autophagy via preventing from the formation of Atg5-12-16L complex to facilitate replication of T. gondii and development of toxoplasmosis.

Keywords: Autophagy; Monocyte cell line; Profilin; Toxoplasma gondii.

MeSH terms

  • Autophagy* / genetics
  • Autophagy-Related Protein 12 / genetics*
  • Autophagy-Related Protein 12 / metabolism
  • Autophagy-Related Protein 5 / genetics*
  • Autophagy-Related Protein 5 / metabolism
  • Autophagy-Related Protein 7 / genetics*
  • Autophagy-Related Protein 7 / metabolism
  • Down-Regulation* / genetics
  • Host-Parasite Interactions / genetics
  • Humans
  • Models, Biological
  • Profilins / metabolism*
  • THP-1 Cells
  • Toxoplasma / metabolism*
  • Up-Regulation* / genetics

Substances

  • ATG12 protein, human
  • ATG5 protein, human
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Profilins
  • ATG7 protein, human
  • Autophagy-Related Protein 7