title: Toxoplasma gondii GRA15IIeffector-induced M1 cells ameliorate liver fibrosis in mice infected with Schistosomiasis japonica.
abstract: Recent studies indicated that type II Toxoplasma gondii (Tg) GRA15IIfavored the generation of classically activated macrophages (M1), whereas type I/III TgROP16I/IIIpromoted 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 TgGRA15IIon mouse hepatic fibrosis with schistosomiasis. The gra15IIand rop16I/IIIgenes were amplified from strains T. gondii PRU and Chinese 1 Wh3, respectively. Lentiviral vectors containing the gra15IIor rop16I/IIIplasmid 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 GRA15II-driven macrophages via the tail vein and infected with S. japonicum cercariae. TgGRA15IIinduced a M1-biased response, whereas TgROP16I/IIIdrove 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 TgGRA15II-activated macrophages. Furthermore, mice inoculated with TgGRA15II-biased macrophages displayed a notable alleviation of collagen deposition and granuloma formation in their liver tissues. Our results suggest that TgGRA15II-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.
authors.affiliation: Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, and Clinical Laboratory of the First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, and Clinical Laboratory of the First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.|Department of Immunology, Anhui Medical University; Hefei 230022, China.|Department of Blood Transfusion, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Laboratory Diagnosis, The Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yan
authors.affiliation: Pediatrics Department of Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.
authors.forename: Shushu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Pediatrics Department of Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, and Clinical Laboratory of the First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.|Intensive Care Unit of Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, and Clinical Laboratory of the First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors.forename: Yuanling
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, and Clinical Laboratory of the First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Laboratory Diagnosis, The Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, and Clinical Laboratory of the First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.|Department of Immunology, Anhui Medical University; Hefei 230022, China.
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, and Clinical Laboratory of the First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors.forename: Deyong
authors.initials: D
authors.lastname: Chu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D008099:Liver / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D008264:Macrophages / Q000469:parasitology / Q000473:pathology*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D015800:Protozoan Proteins / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012554:Schistosomiasis japonica / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology; D014122:Toxoplasma / Q000378:metabolism*
chemical_list: D016207:Cytokines; D015800:Protozoan Proteins; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13