title: Upregulation of PD-1 on CD4⁺CD25⁺ T cells is associated with immunosuppression in liver of mice infected with Echinococcus multilocularis.
abstract: Alveolar echinococcosis is a zoonotic disease caused by Echinococcus multilocularis (E. multilocularis) infection. The relationship between PD-1/PD-L1 pathway and Tregs at different stages of E. multilocularis infection has rarely been reported. This study aims to investigate the role of PD-1/PD-L1 in immunosuppression of Tregs in E. multilocularis infection. Hematoxylin-eosin staining, flow cytometry, immunohistochemistry, quantitative RT-PCR analysis, cytometric bead array and MTT assay were used to analyze liver pathological changes, percentages of PD-1(+) Tregs and PD-L1(+) dendritic cells (DCs), expression levels of PD-1, PD-L1 and Foxp3, levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) and proliferation of lymphocytes. During middle-late stage (day 30 to day 330) the percentages of PD-1(+) Tregs and PD-L1(+) DCs together with levels of Foxp3, IL-10 and TGF-β increased significantly and maintained at high level. The expression of PD-1 and PD-L1 was increased with the enlarging erosion of E. multilocularis, and was mainly distributed in hepatic sinus, fibrous wall of alveolar hydatid and germinal layer around foci of infection. PD-1/PD-L1 promoted the secretion of IL-10 and TGF-β. Our results indicate that engagement of the PD-1 and PD-L1 correlates with inhibition of T-cell effector function, cytokine secretion and proliferation. High expression of PD-1/PD-L1 may play an important role in stimulating CD4(+)CD25(+) T cells, and maintaining peripheral tolerance and immune evasion during chronic infection of E. multilocularis.
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: La
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Pang
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, 251 Xining Road, 810000, Xi-ning, Qinghai, China. Electronic address: fanhaining@medmail.com.cn.
authors.forename: Haining
authors.initials: H
authors.lastname: Fan
authors.affiliation: Xinjiang Laboratory of Hydatid Fundamental Medicine, First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, 830011,Urumqi, Xinjiang, China; Department of Immunology, School of Preclinical Medicine of Xinjiang Medical University 393 Xinyi Road, 830011, Urumqi, Xinjiang, China. Electronic address: 1601379937@qq.com.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D004443:Echinococcosis / Q000276:immunology*; D048210:Echinococcus multilocularis / Q000276:immunology*; D057131:Immune Evasion; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: Echinococcus multilocularis; Infection; PD-1; PD-L1; Tregs