TLR2 directing PD-L2 expression inhibit T cells response in Schistosoma japonicum infection

Yanan Gao; Lin Chen; Min Hou; Yingying Chen; Minjun Ji; Haiwei Wu; Guanling Wu

doi:10.1371/journal.pone.0082480

TLR2 directing PD-L2 expression inhibit T cells response in Schistosoma japonicum infection

PLoS One. 2013 Dec 20;8(12):e82480. doi: 10.1371/journal.pone.0082480. eCollection 2013.

Authors

Yanan Gao¹, Lin Chen², Min Hou², Yingying Chen³, Minjun Ji², Haiwei Wu⁴, Guanling Wu²

Affiliations

¹ 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.
² Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China ; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu, China.
³ Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China.
⁴ Center for International Health Research, Rhode Island Hospital, Providence, Rhode Island, United States of America.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B7-H1 Antigen / metabolism
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / immunology
Dendritic Cells / immunology
Female
Gene Expression Regulation
Immunity, Cellular / immunology
Interferon-gamma / metabolism
Interleukin-10 / metabolism
Lymphocyte Count
Mice, Inbred C57BL
Mice, Knockout
Programmed Cell Death 1 Ligand 2 Protein / metabolism*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Schistosoma japonicum / physiology*
Schistosomiasis japonica / genetics
Schistosomiasis japonica / immunology*
Schistosomiasis japonica / metabolism*
Schistosomiasis japonica / parasitology
T-Lymphocytes / immunology*
Toll-Like Receptor 2 / deficiency
Toll-Like Receptor 2 / genetics
Toll-Like Receptor 2 / metabolism*

Substances

B7-H1 Antigen
Cd274 protein, mouse
Pdcd1lg2 protein, mouse
Programmed Cell Death 1 Ligand 2 Protein
RNA, Messenger
Tlr2 protein, mouse
Toll-Like Receptor 2
Interleukin-10
Interferon-gamma

Grants and funding

This work was supported by the National Basic Research Program of China (973 Program No. 2007CB513102) and the National Natural Science Foundation of China (NSFC) (Project No. 81171593). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.