Toxoplasma gondii GRA15II effector-induced M1 cells ameliorate liver fibrosis in mice infected with Schistosomiasis japonica

• Published in: Cellular & molecular immunology 2018-02, Vol.15 (2), p.120-134
• Main Authors: Xie, Yuanyuan, Wen, Huiqin, Yan, Ke, Wang, Shushu, Wang, Xuesong, Chen, Jian, Li, Yuanling, Xu, Yuanhong, Zhong, Zhengrong, Shen, Jilong, Chu, Deyong
• Format: Article
• Language: English
• Subjects: Antibodies; Biomedical and Life Sciences; Biomedicine; Cell culture; Cell proliferation; Collagen; Effector cells; Fibrosis; Granuloma; Granulomatosis; Hepatocytes; Immune response; Immunology; Immunomodulation; Liver; Macrophages; Medical Microbiology; Microbiology; Pathogenesis; Phenotypes; Polarization; research-article; Rodents; Schistosomiasis; Toxoplasma gondii; Vaccine; Vectors
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2016.21

Recent studies indicated that type II Toxoplasma gondii ( Tg ) GRA15 II favored the generation of classically activated macrophages (M1), whereas type I/III Tg ROP16 I/III promoted the polarization of alternatively activated macrophages (M2). A number of studies have demonstrated that M2 cells are involved in the pathogenesis of the liver fibrogenesis caused by Schistosoma japonicum . The purpose of the present study was to explore the inhibitory effect of Toxoplasma- derived Tg GRA15 II on mouse hepatic fibrosis with schistosomiasis. The gra15 II and rop16 I/III genes were amplified from strains T. gondii PRU and Chinese 1 Wh3, respectively. Lentiviral vectors containing the gra 15 II or rop 16 I/III plasmid were constructed and used to infect the RAW264.7 cell line. The polarization of the transfected cells was evaluated, followed by co-culture of the biased macrophages with mouse hepatic stellate JS1 cells. Then, mice were injected with GRA15 II -driven macrophages via the tail vein and infected with S. japonicum cercariae. Tg GRA15 II induced a M1-biased response, whereas Tg ROP16 I/III drove the macrophages to a M2-like phenotype. The in vitro experiments indicated that JS1 cell proliferation and collagen synthesis were decreased following co-culture with Tg GRA15 II -activated macrophages. Furthermore, mice inoculated with Tg GRA15 II -biased macrophages displayed a notable alleviation of collagen deposition and granuloma formation in their liver tissues. Our results suggest that Tg GRA15 II -induced M1 cells may dampen the M2 dominant pathogenesis of hepatic fibrosis and granulomatosis. These results provide insights into the use of parasite-derived immunomodulators as potential anti-fibrosis agents and to re-balance the schistosomiasis-induced immune response.