Interleukin-23 derived from CD16+ monocytes drives IL-17 secretion by TLR4 pathway in children with mycoplasma pneumoniae pneumonia

Life Sci. 2020 Oct 1:258:118149. doi: 10.1016/j.lfs.2020.118149. Epub 2020 Jul 26.

Abstract

Aims: The study aimed to investigate whether IL-23 is amplified in monocyte subsets of MP pneumonia and to determine its relevant pathway.

Materials and methods: We firstly analyze the IL-23p19 expression in monocyte subgroups in MP pneumonia patients and healthy controls subjects by using flow cytometry. Then, we also analyzed the percentage of IL-17+γδT cells and Th17 cells in patients with MP pneumonia and controls subjects. At the same time, the relation between IL-23 and IL-17 were also assessed. Furthermore, we constructed the recombinant community-acquired respiratory distress syndrome (CARDS) toxin and intend to stimulate peripheral blood mononuclear cells and RAW264.7 cells in vitro. IL-23p19 was detected by flow cytometry and the mRNA levels were measured by real-time PCR. Finally, TLR4 pathway was also investigated by TAK242 inhibitor.

Key findings: It turned out that the expression of IL-23p19 was increased in CD14brightCD16+ monocyte of MP pneumonia patients than controls subjects. The patients with MP pneumonia had significantly higher the percentage of IL-17+γδT cells and Th17 cells than controls subjects. Interestingly, the levels of IL-23 were positively related to IL-17 in MP pneumonia patients. CD16+ monocytes and RAW264.7 cells, respectively can be induced by CARDS toxin to secrete IL-23 by TLR4 pathway in vitro.

Significance: These results indicated that IL-23-IL-17+γδT/Th17 axis may play a role in the pathogenesis of MP pneumonia, whereas IL-23 derived from CD16+ monocytes was expanded in MP pneumonia by TLR4 pathway.

Keywords: IL-17; IL-23; Monocyte; Mycoplasma pneumoniae pneumonia; TLR4.

MeSH terms

  • Animals
  • Child
  • Child, Preschool
  • Female
  • GPI-Linked Proteins / immunology
  • Humans
  • Interleukin-17 / immunology*
  • Interleukin-23 / immunology*
  • Male
  • Mice
  • Monocytes / immunology
  • Monocytes / pathology
  • Mycoplasma pneumoniae / immunology*
  • Pneumonia, Mycoplasma / immunology*
  • Pneumonia, Mycoplasma / pathology
  • RAW 264.7 Cells
  • Receptors, IgG / immunology*
  • Signal Transduction
  • Toll-Like Receptor 4 / immunology*

Substances

  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Interleukin-17
  • Interleukin-23
  • Receptors, IgG
  • Toll-Like Receptor 4