Excretory/secretory proteins from Trichinella spiralis adult worms alleviate myocardial dysfunction induced by sepsis in murine models

Abstract

Sepsis-induced myocardial dysfunction (SIMD) is a hazardous symptom of sepsis and causes significant death rates. Although previous research has shown that helminthic derivatives alleviate disorders, the immunomodulatory functions of excretory/secretory proteins from Trichinella spiralis adult worms (Ts-AES) in SIMD have not yet been identified. We wanted to see how Ts-AES affects SIMD in this work and explore the potential immune mechanism involved. Murine sepsis model was established by cecal ligation and puncture (CLP) in male BALB/C mice. Following CLP surgery, each mouse received 20 μg Ts-AES intraperitoneally. Results showed that administration of Ts-AES improved the 72-h survival rate of septic mice by up to 40 % compared to untreated mice, who all died within the period. The SIMD was greatly alleviated, characterized by significantly improved left ventricle functions during systole and diastole, reduced biventricular enlargement, and myocardial injury scores. Upon histopathological examination, Ts-AES treatment greatly reduced cardiac inflammation and pathologic injury. The immunomodulatory effect of Ts-AES on protecting SIMD was associated with M2-type macrophage polarization that induces immunomodulatory cytokines and lowers pro-inflammatory cytokines, potentially by blocking the HMGB1/TLR2/NF-κB signal pathway. Our findings in this study demonstrate the potential of Ts-AES as a therapeutic agent for SIMD or other inflammatory disorders.