Trichinella spiralis Excretory-Secretory Products Protect against Polymicrobial Sepsis by Suppressing MyD88 via Mannose Receptor

Trichinella spiralis (T. spiralis) or its excretory-secretory products (TsES) protect hosts from autoimmune diseases, which depend on inducing host T helper (Th) 2 immune response and inhibiting inflammatory factors. Sepsis is a systemic inflammatory response syndrome (SIRS) evoked by infection. Little is known about the effects of helminths or their excretory-secretory products on sepsis. Here, we investigated the effects of TsES in a mice model of polymicrobial sepsis. TsES improved survival, reduced organ injury, and enhanced bacterial clearance in septic mice. To investigate the molecular mechanism, macrophages from septic patients or the control group were incubated with TsES. TsES reduced sepsis-inducing inflammatory cytokines mediated by Toll-like receptors (TLR) in vitro by suppressing TLR adaptor-transducer myeloid differentiation factor 88 (MyD88) and nuclear factor- (NF-)-kappa B. Furthermore, TsES upregulated mannose receptor (MR) expression during sepsis. MR blocking attenuated the effects of TsES on MyD88 and NF-kappa B expression. In vivo, MR RNAi reduced the survival rate of septic mice treated with TsES, suggesting that TsES-mediated protection against polymicrobial sepsis is dependent on MR. Thus, TsES administration might be a potential therapeutic strategy for treating sepsis.

旋毛虫（T. spiralis）及其排泄 - 分泌产物（TsES）可保护宿主免受自身免疫性疾病的侵害，这依赖于诱导宿主辅助性T细胞（Th）2免疫反应并抑制炎症因子。脓毒症是一种由感染引发的全身性炎症反应综合征（SIRS）。关于蠕虫及其排泄 - 分泌产物对脓毒症的影响知之甚少。在此，我们研究了TsES在多微生物脓毒症小鼠模型中的作用。TsES提高了脓毒症小鼠的存活率，减轻了器官损伤，并增强了细菌清除能力。为了探究其分子机制，将脓毒症患者或对照组的巨噬细胞与TsES一起培养。TsES在体外通过抑制Toll样受体（TLR）的衔接蛋白 - 转导子髓样分化因子88（MyD88）和核因子 - κB（NF - κB），减少了由Toll样受体介导的脓毒症诱导性炎症细胞因子。此外，TsES在脓毒症期间上调了甘露糖受体（MR）的表达。MR阻断减弱了TsES对MyD88和NF - κB表达的影响。在体内，MR RNA干扰降低了用TsES治疗的脓毒症小鼠的存活率，表明TsES介导的对多微生物脓毒症的保护作用依赖于MR。因此，TsES给药可能是治疗脓毒症的一种潜在治疗策略。