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Delayed IL-12 production by macrophages during Toxoplasma gondii infection is regulated by miR-187

Abstract

Toxoplasma gondii is an important zoonotic protozoan worldwide which infects most of warm-blooded mammals and birds, including human, and cause toxoplasmosis. As an intracellular parasite, T. gondii must evade host immune surveillance, such as IL-12 and IFN-γ, in order to survive and multiply in macrophages and other host cells. By delaying IL-12 secretion of host macrophages within 24 h after infection, T. gondii ensures not only self-survival but also the establishment of chronic infection of host cells. MicroRNA plays an important role in regulating gene transcription and translation. The mechanisms of IL-12 production during T. gondii infection are still unknown. Thus, understanding how the parasites manipulate IL-12 production by host macrophage is critical for the effective prevention and therapy of T. gondii infection. In the present study, regulation of delayed macrophage IL-12 production during T. gondii infection was explored. We found that the production of IL-12 after T. gondii infection was inhibited during the first 24 h and then resumed. The expression pattern of miR-187 production was consistent with the production pattern of IL-12 during T. gondii infection. The downregulation of miR-187 promoted Akt and P65 phosphorylation and delayed IL-12 production at late stage (after 24 h) of T. gondii infection. Dual-luciferase reporter assay indicated that MiR-187 targeted the NFKBIZ gene. Our results suggested that the delayed IL-12 production in mouse macrophages during T. gondii infection was regulated by miR-187.

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Funding

This research was funded by the Jilin Key Scientific and Technological Development Program (20130206023NY).

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JL and GL were responsible for the experimental design. HJ, TZ, YY, XL, and PG planned and performed the experiments. HJ, TZ, YY, and PG drafted the main manuscript and performed the data analysis. GL, XZ, and JL were responsible for guiding and supporting the experiments and revising the manuscript. All authors read and approved the final manuscript.

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Correspondence to Guojiang Li or Jianhua Li.

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Jiang, H., Zhai, T., Yu, Y. et al. Delayed IL-12 production by macrophages during Toxoplasma gondii infection is regulated by miR-187. Parasitol Res 119, 1023–1033 (2020). https://doi.org/10.1007/s00436-019-06588-0

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  • DOI: https://doi.org/10.1007/s00436-019-06588-0

Keywords

  • T. gondii
  • IL-12
  • miRNAs
  • Akt
  • NF-κB