Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2019; 25(45): 6634-6652
Published online Dec 7, 2019. doi: 10.3748/wjg.v25.i45.6634
Toxoplasma ROP16I/III ameliorated inflammatory bowel diseases via inducing M2 phenotype of macrophages
Yong-Wei Xu, Rui-Xin Xing, Wen-Hui Zhang, Lu Li, Yi Wu, Jing Hu, Cong Wang, Qing-Li Luo, Ji-Long Shen, Xi Chen
Yong-Wei Xu, Rui-Xin Xing, Wen-Hui Zhang, Lu Li, Yi Wu, Jing Hu, Xi Chen, Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Cong Wang, Qing-Li Luo, Ji-Long Shen, Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Zoonoses Anhui, Anhui Medical University, Hefei 230032, Anhui Province, China
Author contributions: Chen X, Sheng JL and Xu YW conceived and designed the trial; Xu YW, Li L, Xing RX and Wu Y performed the experiments; Xu YW, Zhang WH, Hu J, Wang C and Luo QL analysed the data; Xu YW wrote the manuscript; Chen X, Sheng JL and Xu YW critically revised the manuscript; All authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81471983; the Key Research and Development Plan Project of Anhui Province, Department of Science and Technology 2019, No. 201904a07020043; the Key Project of Natural Science Research in the Universities of Anhui Provence, No. KJ2017A202; and the Research Fund Project of Anhui Institute of Transforming Medicine, No. 2017zhyx04.
Institutional review board statement: This study does not involve human and animal subjects.
Institutional animal care and use committee statement: No animal models were used in this study.
Conflict-of-interest statement: None of the authors has any conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xi Chen, MD, PhD, Chief Doctor, Dean, Director, Professor, Senior Researcher, Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, No. 218 Ji Xi Road, Hefei 230022, Anhui Province, China.
Telephone: +86-551-65908802 Fax: +86-551-65908802
Received: August 9, 2019
Peer-review started: August 9, 2019
First decision: September 19, 2019
Revised: October 3, 2019
Accepted: November 13, 2019
Article in press: November 13, 2019
Published online: December 7, 2019
Processing time: 118 Days and 22.1 Hours
Research background

Inflammatory bowel disease (IBD) is characterized by chronic and non-specific inflammation of the intestinal mucosa and mainly includes ulcerative colitis and Crohn's disease. The incidence of IBD is increasing, and the disease has gained growing attention due to its substantial impacts on patient quality of life and increased side effects of traditional drugs in the treatment of IBD, so it is important to find new methods to treat IBD.

Research motivation

Toxoplasma ROP16I/III(ToxoROP16I/III) induced RAW264.7 polarization to M2 macrophage, down-regulated the M1-associated inflammation response and played a protective role in Caco-2 intestinal epithelial cells.

Research objectives

The pathogenesis of IBDs remains unclear and the efficacy of current treatments is uncertain. Toxoplasma ROP16I/III-induced M2 macrophages might provide a promising strategy for the immunotherapy of IBDs using the parasite-derived molecules.

Research methods

ToxoROP16I/III induced RAW264.7 polarization to M2 macrophage, enhanced the synthesis of arginase-1 (Arg-1), interleukin (IL)-10, transformed growth factor (TGF)-β1, and IL-13, down-regulated the M1-associated inflammation response IL-1β, tumor necrosis factor (TNF)-α, IL-6, nitric oxide (NO), and inducible nitric oxide synthase (iNOS) as shown by quantitative real-time reverse transcriptase polymerase chain reaction. M1 and M2 cells co-cultured with Caco-2 cells through transwell alleviated Caco-2 cell apoptosis and its associated proteins by flow cytometry assay and Western blotting.

Research results

M1 cells exhibited dramatically increased production of iNOS, NO, TNF-α, IL-1β, and IL-6, while ToxoROP16I/III induced macrophage bias to M2 cells in vitro, showing increased expression of Arg-1, IL-10, and TGF-β1 and elevated production of p-Stat3 and p-Stat6. The M2 mixed with M1 cell culture downregulated the production of iNOS, NO, TNF-α, IL-1β, and IL-6 by M1 cells, resulting in apoptotic alleviation of Caco-2 cells.

Research conclusions

ToxoROP16I/III-induced macrophages with an M2 phenotype inhibited the apoptosis of Caco-2 cells caused by lipopolysaccharide macrophage stimulation. These findings may be helpful for gaining a better understanding of the underlying mechanism and may represent a promising strategy for a novel immunotherapy against IBD.

Research perspectives

ToxoROP16I/III may be a new method for the treatment of IBD, and there are few side effects in the course of treatment. It will become another new aspect of study in the treatment of IBD.