Trichinella spiralis excretory-secretory products protect against polymicrobial sepsis by suppressing MyD88 via mannose receptor

Linlin Du  ¹ , Lihua Liu  ² , Yang Yu  ¹ , Hui Shan  ¹ , Leiqing Li  ¹

Affiliations

• ¹ Department of Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China.
• ² Department of Respiratory Disease, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China.

Abstract

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-)-κB. Furthermore, TsES upregulated mannose receptor (MR) expression during sepsis. MR blocking attenuated the effects of TsES on MyD88 and NF-κB 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.