CD4+CD25+ Treg induction by an HSP60-derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent.
Chronic schistosome infection results in the suppression of host immune responses, allowing long-term schistosome survival and restricting pathology. Current theories suggest that Treg play an important role in this regulation. However, the mechanism of Treg induction during schistosome infection is still unknown. The aim of this study was to determine the mechanism behind the induction of CD4(+)CD25(+) T cells by Schistosoma japonicum HSP60 (SjHSP60)-derived peptide SJMHE1 as well as to elucidate the cellular and molecular basis for the induction of CD4(+)CD25(+) T cells during S. japonicum infection. Mice immunized with SJMHE1 or spleen and LN cells from naïve mice pretreated with SJMHE1 in vitro all displayed an increase in CD4(+)CD25(+) T-cell populations. Release of IL-10 and TGF-beta by SJMHE1 stimulation may contribute to suppression. Adoptively transferred SJMHE1-induced CD4(+)CD25(+) T cells inhibited delayed-type hypersensitivity in BALB/c mice. Additionally, SJMHE1-treated APC were tolerogenic and induced CD4(+) cells to differentiate into suppressive CD4(+)CD25(+) Treg. Furthermore, our data support a role for TLR2 in SJMHE1-mediated CD4(+)CD25(+) Treg induction. These findings provide the basis for a more complete understanding of the S. japonicum-host interactions that contribute to host homeostatic mechanisms, preventing an excessive immune response.
Wang
Xuefeng
X
Department of Pathogen Biology & Immunology, Department of Pharmacology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Zhou
Sha
S
Chi
Ying
Y
Wen
Xiaoyun
X
Hoellwarth
Jason
J
He
Lei
L
Liu
Feng
F
Wu
Calvin
C
Dhesi
Shawn
S
Zhao
Jiaqing
J
Hu
Wei
W
Su
Chuan
C
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006790:Host-Parasite Interactions / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012549:Schistosoma japonicum / Q000276:immunology; D012554:Schistosomiasis japonica / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D000947:Antigens, Helminth; D018834:Chaperonin 60; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2