title: TLR2 directing PD-L2 expression inhibit T cells response in Schistosoma japonicum infection.
abstract: Toll-like receptor 2 (TLR2) was shown to be an important immune receptor involved in the recognition of schistosome antigens, especially soluble egg antigen (SEA). In mice models with Schistosoma japonicum acute infection, we observed enhanced T cell-mediated immune responses in TLR2 knock out (TLR2(-/-)) mice compared with B6 mice. In Schistosoma japonicum chronic infection models, programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) expression as well as TLR2 expression gradually increased in B6 mice, while only PD-L2 expression significantly decreased in TLR2(-/-) mice. Meanwhile, Programmed Death 1(PD-1) expression on CD4(+)T cells was down-regulated in TLR2(-/-) mice after a large number of egg appeared. We also found that stimulation with schistosome antigens, especially SEA, could up-regulate PD-L2 expression on BMDCs in a TLR2-dependent manner in vitro. Schistosome antigens primed-BMDCs with impaired expression of TLR2 or PD-L2 could induce CD4(+)T cells to produce low level of IL-10 or high level of IFN-γ. Our results indicated that TLR2 signaling can direct PD-L2 expression on DCs, which binds to PD-1 mainly on CD4(+)T cells, to help inhibit T cells response in Schistosoma japonicum infection.
authors.affiliation: Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China ; Department of Pathogen Biology and Immunology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China ; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China ; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China ; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Ji
authors.affiliation: Center for International Health Research, Rhode Island Hospital, Providence, Rhode Island, United States of America.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China ; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu, China.
authors.forename: Guanling
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012549:Schistosoma japonicum / Q000502:physiology*; D012554:Schistosomiasis japonica / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D007371:Interferon-gamma