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

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.

Succinate coenzyme A ligase β‐like protein from Trichinella spiralis is a potential therapeutic molecule for allergic asthma

“…In our previous investigation, we observed an elevation in the serum level of IL‐9 antibody in T. spiralis infected mice following pET‐32a treatment; however, this increase was not statistically significant when compared to the blank control group. 20 The findings of this study imply that pET‐32a potentially modulates the secretion of IL‐9; however, further investigation is warranted to elucidate the precise regulatory mechanism in future studies. Our findings clearly demonstrate that the rTS‐SUCLA‐β protein obtained from T. spiralis , has the ability to alleviate airway inflammation in a mouse model of OVA‐induced asthma by facilitating the activation of the host immune system.…”

“…Escherichia coli BL21 (Vazyme Nanjing) transformed with pET‐32a (+)/TS‐SUCLA‐β was induced, and the rTS‐SUCLA‐β was purified as previously described. 20 The protein labeled with histidine in pET‐32a was also prepared using the identical method mentioned earlier, serving as a control protein for subsequent functional analysis. A ToxinEraser TM Endotoxin Removal Kit (GenScript) was employed to eliminate lipopolysaccharide from the Ts‐SUCLA‐β protein.…”

“… 19 Our previous study found that rTs‐SUCLA‐β can bind to rat peripheral blood mononuclear cells (PBMCs) and significantly inhibit the proliferation rate, migration, and monocyte phagocytosis of PBMCs. 20 In vivo, inhibition of IL‐17A secretion and a significant increase in levels of anti‐rTs‐SUCLA‐β immunoglobulin (IgG, IgG1, and IgG2a) promoted a significant reduction in ML of T. spiralis . 20 The findings indicate that rTs‐SUCLA‐β has the potential to serve as a promising candidate for managing T. spiralis infection through its ability to suppress immune cell activity and decrease parasite load.…”

“… 20 In vivo, inhibition of IL‐17A secretion and a significant increase in levels of anti‐rTs‐SUCLA‐β immunoglobulin (IgG, IgG1, and IgG2a) promoted a significant reduction in ML of T. spiralis . 20 The findings indicate that rTs‐SUCLA‐β has the potential to serve as a promising candidate for managing T. spiralis infection through its ability to suppress immune cell activity and decrease parasite load. Moreover, it could potentially be utilized in the treatment of autoimmune disorders and prevention of organ transplant rejection by inhibiting the host's IL‐17A immune response.…”

Trichinella pseudospiralis-secreted 53 kDa protein ameliorates imiquimod-induced psoriasis by inhibiting the IL-23/IL-17 axis in mice

“…Our previous study indicated that T. pseudospiralis infection decreased the expression of Il17a , Il1b and Il6 in the pathological tissues and splenocytes of EAE model mice [ 2 ]. Some Trichinella -derived proteins have been confirmed to inhibit IL-17 production in PBMCs, such as succinate coenzyme A ligase beta-like protein (SUCLA-β) [ 49 ]. TsP53 has been confirmed to be anti-inflammatory by its suppressive effects on DCs and macrophages [ 16 , 26 , 50 ].…”