Succinate Coenzyme A Ligase Beta-Like Protein from Trichinella spiralis Suppresses the Immune Functions of Rat PBMCs in Vitro and Inhibits the Secretions of Interleukin-17 in Vivo.

Sun Sun,Song Song,Li Li,Yan Yan,Xu Xu,Naqvi Naqvi,Chu Chu

doi:10.3390/vaccines7040167

Abstract

Succinate Coenzyme A ligase beta-like protein (SUCLA-β) is a subunit of Succinyl-coenzyme A synthetase, which is involved in substrate synergism, unusual kinetic reaction in which the presence of SUCLA-β for one partial reaction stimulates another partial reaction. Trichinella spiralis is a parasitic nematode, which may hinder the development of autoimmune diseases. Immunomodulatory effects of SUCLA-β from Trichinella spiralis in the parasite-host interaction are unidentified. In this study the gene encoding T. spiralis SUCLA-β was cloned and expressed. Binding activities of recombinant T. spiralis SUCLA-β (rTs-SUCLA-β) to rat peripheral blood mononuclear cells (PBMCs) were checked by immunofluorescence assay (IFA) and the immuno-regulatory effects of rTs-SUCLA-β on cell migration, cell proliferation, nitric oxide (NO) production and apoptosis were observed by co-incubation of rTs-SUCLA-β with rat PBMCs in vitro, while cytokine secretions in rTs-SUCLA-β treated rats were evaluated in vivo. Furthermore, phagocytosis of monocytes was detected by flow cytometry and effects of rTs-SUCLA-β-induced protective immunity on T. spiralis adult worms and muscle larva were evaluated in rats. The IFA results revealed that rTs-SUCLA-β could bind to rat PBMCs. Treatment of PBMCs with rTs-SUCLA-β significantly decreased the monocyte phagocytosis, cell migration and cell proliferation, while NO production and apoptosis of PBMCs were unaffected. Results of the in vivo study showed that the IL-17 secretion decreased significantly after rTs-SUCLA-β administration in rats, while no significant effects were observed on the secretions of IFN-γ, IL-9, TGF-β and IL-4. Moreover, significant reduction of T. spiralis muscle larvae burden and significant increase in anti-rTs-SUCLA-β immunoglobulin level of IgG, IgG1 and IgG2a was observed in rTs-SUCLA-β-administered rats. The results indicated that rTs-SUCLA-β may be a potential target for controlling T. spiralis infection by suppressing the immune functions of the rat PBMCs and by reducing the parasite burden. Additionally it may also contribute to the treatment of autoimmune diseases and graft rejection by suppressing IL-17 immune response in the host.

Highlights

The immune system is a defense mechanism in the body that involves peripheral blood mononuclear cells (PBMCs)
Western blot analysis showed that rTs-SUCLA-β protein could be recognized by serum from mice experimentally infected with T. spiralis (Figure 2A, Lane 1) and be recognized by anti-rTs-SUCLA-β polyclonal antibodies (Figure 2B, Lane 1)
The results indicated that rTs-SUCLA-β had good antigenicity and could be recognized by immune system of host

Summary

Introduction

The immune system is a defense mechanism in the body that involves peripheral blood mononuclear cells (PBMCs). Trichinella spiralis (T. spiralis) is a zoonotic nematode that causes chronic infection in a wide range of mammalian hosts [4] It can hinder development of autoimmune diseases and other inflammatory disorders by creating an anti-inflammatory environment [5]. T. spiralis has ability to build their home within the body of host by transforming infected muscle cells into new type of cells, the so-called nurse cell [7,8]. Intracellular localization of these parasites takes place at skeletal muscle cells and enterocytes, which are known as habitat of this parasite [9]. Because of economic hurdles in these preventive measures, a vaccine for veterinary use is best alternative to prevent humans by adding in animal feed

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