Schistosoma japonicum HSP60-derived peptide SJMHE1 suppresses delayed-type hypersensitivity in a murine model.

Xuefeng Wang,Jun Wang,Chengcheng Xu,Yuepeng Zhou,Liang Shi,Chaoming Mao,Yong Liang,Hongchang Ni,Yuting Su,Xiao Mou,Deyu Chen

doi:10.1186/s13071-016-1434-4

Abstract

BackgroundParasite-derived molecules with immunomodulatory properties, which have been optimised during host-parasite co-evolution, exhibit potential applications as novel immunotherapeutics. We have previously demonstrated that Schistosoma japonicum HSP60-derived peptide SJMHE1 induces CD4+CD25+ regulatory T-cells (Tregs) and that adoptively transferred SJMHE1-induced CD4+CD25+ Tregs inhibit delayed-type hypersensitivity (DTH) in mice. However, multiple concerns regarding this method render this treatment unsuitable. To gain further insights into the potential effects of SJMHE1, we used ovalbumin (OVA)-induced DTH and evaluated the effect of SJMHE1 on DTH mice.MethodsBALB/c mice were sensitised with OVA alone or combined with SJMHE1 and then challenged with OVA to induce DTH. We first analysed the potential effects of SJMHE1 by measuring DTH responses, T-cell responses, cytokine secretion, and Treg proportions. We then evaluated the expression levels of IL-10 and TGF-β1 in CD4+CD25+ T-cells during DTH and Treg generation to identify the mechanism by which SJMHE1 suppresses DTH.ResultsSJMHE1 modulated the effector response against OVA-induced DTH and stimulated the production of the anti-inflammatory cytokines IL-10 and TGF-β1 in immunised mice through a mechanism involving CD4+CD25+ Tregs. SJMHE1-induced CD4+CD25+ Tregs expressed high levels of CTLA-4, IL-10, and TGF-β1, which substantially contributed to the suppressive activity during DTH. The administration of SJMHE1 to DTH in mice led to the expansion of CD4+CD25+ Tregs from CD4+CD25− T-cells in the periphery, which inhibited DTH responses.ConclusionsOur study proves that the parasite-driven peptide suppresses DTH in mice, which may confer a new option for inflammation treatment.

Highlights

Parasite-derived molecules with immunomodulatory properties, which have been optimised during host-parasite co-evolution, exhibit potential applications as novel immunotherapeutics
We investigated the potential effects of SJMHE1 on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) to develop the medical potential of the therapeutic peptide and to elucidate the mechanism by which SJMHE1-induced CD4+CD25+ cells downregulate DTH responses
Considering that 30 μg of SJMHE1 induced the strongest inhibition of DTH response, we investigated local cytokine production in the DTH ears from mice primed with OVA alone or combined with 30 μg of SJMHE1

Summary

Introduction

Parasite-derived molecules with immunomodulatory properties, which have been optimised during host-parasite co-evolution, exhibit potential applications as novel immunotherapeutics. Instead of infecting people with pathogens, which predisposes them to the inevitable risk of side effects, a more responsible approach is to identify the immunomodulatory molecules that selectively mimic the desirable effects of infection and use them as a novel therapeutic approach [6, 15, 16]. Data from animal models (and to a lesser extent, human studies) show that helminths release products that interfere with the development of allergic responses and inflammatory diseases [11, 17, 18]. Considerable studies have focused on identifying novel products that exhibit similar properties. Beneficial products are expected to be identified, characterised, and tested in vivo in the near future

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