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Front. Microbiol. | doi: 10.3389/fmicb.2018.02822

Risk Assessment of Etanercept in Mice Chronically Infected with Toxoplasma gondii

 Jing Yang1, Luyao Wang1, Senyang Li1, Fen Du2, 3, Lixia Wang3,  Junlong Zhao1 and  Rui Fang1*
  • 1Huazhong Agricultural University, China
  • 2Hubei Provincial Center for Diseases Control and Prevention, China
  • 3Hubei Provincial Center for Diseases Control and Prevention, China

Toxoplasma gondii (T. gondii) is a zoonotic parasite that severely harms the health of the host. The cysts of T. gondii can reactivate from bradyzoites to tachyzoites, if the individual develops low or defective immunity, causing lethal toxoplasmosis. The host resists T. gondii infection by mediating Th1-type cellular immunity to generate pro-inflammatory cytokines. Tumor necrosis factor (TNF) is an important pro-inflammatory cytokine, which can induce lysosomal fusion of parasitophorous vacuole to kill parasites. Etanercept is a soluble TNF receptor fusion protein, which is widely used clinically to cure autoimmune diseases. The effects and specific molecular mechanisms of etanercept treatment on patients co-infected with autoimmune diseases and chronic toxoplasmosis are rarely reported. In our study, a mouse model of chronic infection with T. gondii and murine macrophages RAW264.7 cells infected with T. gondii were employed to investigate the impact of etanercept on the status of chronic infection. The cytokines levels and a series of phenotypic experiments in vivo and in vitro were measured. In the present study, the expression levels of TNF, IL-1β and IL-6 were decreased and the brain cysts number was increased in mice chronically infected with T. gondii after being treated with etanercept. In vivo experiments confirmed that etanercept caused a decrease in the immune levels of the mice and activated the brain cysts, which would lead to conversion from chronic infection to acute infection, causing severe clinical and pathological symptoms. Murine macrophages RAW264.7 cells were pretreated with etanercept, and then infected with T. gondii. In vitro experiments, the expression levels of cytokines were decreased, indicating that etanercept could also reduce the cells’ immunity and promote the transformation of bradyzoites to tachyzoites, but did not affect the intracellular replication of tachyzoites. In summary, etanercept treatment could activate the conversion of bradyzoites to tachyzoites through reducing host immunity in vivo and in vitro. The results obtained from this study suggest that the use of etanercept in patients co-infected with autoimmune diseases and chronic toxoplasmosis may lead to the risk of activation of chronic infection, resulting in severe acute toxoplasmosis.

Keywords: Toxoplama gondii, Tumor necorosis factor(TNF), etanercept, Chronic infection, brain cysts reactivation

Received: 16 Aug 2018; Accepted: 02 Nov 2018.

Edited by:

Lisa Sedger, University of Technology Sydney, Australia

Reviewed by:

Rossiane C. Vommaro, Universidade Federal do Rio de Janeiro, Brazil
Ian A. Clark, Australian National University, Australia
Victoria Jeffers, School of Medicine, Indiana University Bloomington, United States  

Copyright: © 2018 Yang, Wang, Li, Du, Wang, Zhao and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Rui Fang, Huazhong Agricultural University, Wuhan, China,