Inonotus obliquus polysaccharide protects against adverse pregnancy caused by Toxoplasma gondii infection through regulating Th17/Treg balance via TLR4/NF-κB pathway

Int J Biol Macromol. 2020 Mar 1;146:832-840. doi: 10.1016/j.ijbiomac.2019.10.051. Epub 2019 Nov 11.

Abstract

The study aimed to explore the protective effects of Inonotus obliquus polysaccharide (IOP) on adverse pregnancy caused by Toxoplasma gondii (T. gondii) infection and discover its potential mechanisms in pregnant mice. Our data showed that IOP significantly reduced the abortion rate, inhibited the decreases of progesterone (P) and estriol (E3) levels and the increase of malondialdehyde (MDA) level, and increased the activities of superoxide dismutase (SOD) and glutathione (GSH). In addition, IOP inhibited the production of inflammatory cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-γ, IL-1β and IL-17A; and promoted the production of anti-inflammatory cytokine IL-10 and transforming growth factor (TGF)-β in T. gondii-infected pregnant mice. Furthermore, IOP effectively up-regulated the expression of forkhead box (Fox)p3, whereas down-regulated the expressions of retinoic acid-related orphan receptor (ROR)γt, signal transducer and activator of transcription (STAT)3 and toll-like receptor (TLR)4, and inhibited the phosphorylations of nuclear factor-κappaB (NF-κB) p65 and inhibitor kappa(Iκ)Bα in placental tissues with T. gondii-infected mice. These findings demonstrate that IOP exerts protective effects against adverse pregnancy caused by T. gondii infection in mice by promoting the balance of T helper (Th)17/regulatory T (Treg) through regulating TLR4/NF-κB pathway.

Keywords: Abortion; Inonotus obliquus polysaccharide; TLR4/NF-κB; Th17/Treg; Toxoplasma gondii.

MeSH terms

  • Abortion, Spontaneous
  • Animals
  • Basidiomycota / chemistry
  • Cytokines / blood
  • Estradiol / blood
  • Female
  • Gene Expression Regulation / drug effects
  • Glutathione / metabolism
  • Malondialdehyde / metabolism
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism*
  • Placenta / metabolism
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*
  • Pregnancy
  • Pregnancy Complications, Parasitic / drug therapy*
  • Pregnancy Complications, Parasitic / immunology
  • Pregnancy Complications, Parasitic / parasitology
  • Pregnancy Complications, Parasitic / prevention & control
  • Progesterone / blood
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Toll-Like Receptor 4 / metabolism*
  • Toxoplasma / physiology*
  • Toxoplasmosis / blood
  • Toxoplasmosis / complications*
  • Toxoplasmosis / genetics
  • Toxoplasmosis / immunology

Substances

  • Cytokines
  • NF-kappa B
  • Polysaccharides
  • RNA, Messenger
  • Toll-Like Receptor 4
  • Progesterone
  • Estradiol
  • Malondialdehyde
  • Superoxide Dismutase
  • Glutathione