Toxoplasma gondii excretory/secretory antigens (TgESAs) suppress pro-inflammatory cytokine secretion by inhibiting TLR-induced NF-κB activation in LPS-stimulated murine macrophages.

Shuai Wang,Xiangrui Li,Ruofeng Yan,Lixin Xu,Javaid Ali Gadahi,Qing Xie,Zhenchao Zhang,Yujian Wang,Xiaokai Song

doi:10.18632/oncotarget.19362

Shuai Wang, Xiangrui Li + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.19362

Copy DOI

Abstract

Excretory/secretory antigens (ESAs) produced by Toxoplasma gondii enable this parasite to invade and survive within the host cells through immunomodulation. In this study, the modulating effects of T. gondii excretory/secretory antigens (TgESAs) on the Ana-1 murine macrophage cell line were evaluated. Ana-1 cells were incubated with several concentrations of TgESAs, and the resulting effects on cellular viability, phagocytotic ability, and apoptosis induction were determined. Pro-inflammatory and anti-inflammatory cytokine secretion, nitric oxide production, toll-like receptor expression, and nuclear translocation of NF-κB were all measured after incubation with TgESAs. After TgESAs treatment, the proliferation and phagocytosis ability of Ana-1 cells decreased, and apoptosis was induced in a dose dependent manner. Analysis of Ana-1 cell culture supernatants showed that TgESAs not only upregulated secretion of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-β1), they also inhibited secretion of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Additionally, TgESAs inhibited nitric oxide production, toll-like receptor (TLR) 2 and 4 activation, and the nuclear translocation of NF-κB in lipopolysaccharide-stimulated Ana-1 macrophages. These results suggest TgESAs inhibit the functional activity of Ana-1 murine macrophages by inhibiting TLR-induced NF-κB activation, which suppresses pro-inflammatory cytokine secretion.

Highlights

Toxoplasmosis is caused by Toxoplasma gondii, which is widespread in humans and animals and is an opportunistic pathogen infecting patients that are immunocompromised [1]
T. gondii excretory/secretory antigens (TgESAs) inhibited nitric oxide production, toll-like receptor (TLR) 2 and 4 activation, and the nuclear translocation of NF-κB in lipopolysaccharide-stimulated Ana-1 macrophages. These results suggest TgESAs inhibit the functional activity of Ana-1 murine macrophages by inhibiting TLRinduced NF-κB activation, which suppresses pro-inflammatory cytokine secretion
During T. gondii infection, the parasite releases a number of molecules termed T. gondii excretory/secretory antigens (TgESAs) into its surrounding environment, which enables the organism invade and survive within the host cells through immunomodulation [2]

Summary

Introduction

Toxoplasmosis is caused by Toxoplasma gondii, which is widespread in humans and animals and is an opportunistic pathogen infecting patients that are immunocompromised [1]. During T. gondii infection, the parasite releases a number of molecules termed T. gondii excretory/secretory antigens (TgESAs) into its surrounding environment, which enables the organism invade and survive within the host cells through immunomodulation [2]. These TgESAs might be one of the first targets of the host’s immune system, and could be a valuable candidate for toxoplasmosis diagnosis and useful for the development of immunization strategies [36]. Macrophages, a target for immunomodulation by the T. gondii, play a critical role in initiating and modulating the host immune response to T. gondii infection. We www.impactjournals.com/oncotarget examined the effect of TgESAs on modulating Ana-1 macrophage activities, which laied the foundation for further understanding of the effective immune-evasion mechanism used by T. gondii

Methods

Results

Conclusion