Abstract
Acute lung injury (ALI) is a common complication of systemic inflammation or sepsis with high morbidity and mortality. Although many studies have confirmed that helminth-derived proteins had strong immunomodulatory functions and could be used to treat inflammatory diseases, there is no report on the therapeutic effect of excretory-secretory products of Trichinella spiralis adult worms (Ts-AES) on sepsis-induced ALI. In this study, the therapeutic efficacy of Ts-AES on sepsis-induced ALI and the underlying immunological mechanism and the signaling pathway were investigated. The results indicated that after being treated with Ts-AES, the survival rate of mice with CLP-induced sepsis was significantly increased to 50% for 72 hours after CLP surgery compared to PBS control group with all mice died. The sepsis-induced ALI was largely mitigated characterized by reduced inflammation cell infiltration and pathological changes in lung tissue, with decreased lung injury scores and lung wet/dry weight ratio. The therapeutic efficacy of Ts-AES is associated with stimulated Tregs response with increased regulatory cytokines IL-10 and TGF-β and downregulated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). The expression of HMGB1, TLR2 and MyD88 in lung tissue was inhibited after treatment of Ts-AES. Our results demonstrated that Ts-AES play an important role in immunomodulation and confer a therapeutic effect on sepsis-induced ALI through inhibiting pro-inflammatory cytokines. The activation of Tregs and increased level of regulatory cytokines IL-10 and TGF-β are possibly involved in the immunomodulatory functions of Ts-AES through HMGB1/TLR2/MyD88 signal pathway. The findings suggest Ts-AES is a potential therapeutic agent for prevention and treatment of sepsis-induced ALI and other inflammatory diseases.
Highlights
Sepsis is life-threatening organ dysfunction caused by a dysregulated severe host immune response to an infection (Singer et al, 2016)
We explored the therapeutic effect of ES products from T. spiralis adult worms (Ts-AES) on CLPinduced septic Acute lung injury (ALI) in BALB/c mice and we found that treatment with Ts-AES significantly improved the survival rate against systematic sepsis and reduced the sepsis-induced ALI in mouse model, providing a potential treatment method to control sepsis-induced ALI and death
To determine whether the High mobility group box 1 protein (HMGB1)/TLR2/MyD88 signaling pathway is involved in the therapeutic effect of Ts-AES on sepsis-induced ALI, we evaluated protein and mRNA expression levels of HMGB1, TLR2 and MyD88 in lung tissue 12 h after Cecal Ligation and Puncture (CLP) surgery
Summary
Sepsis is life-threatening organ dysfunction caused by a dysregulated severe host immune response to an infection (Singer et al, 2016). It has been shown that HMGB1 was elevated in the sera of septic patients, suppressing HMGB1 levels by pharmacological intervention and reducing CLP-induced sepsis mortality (Rosas-Ballina et al, 2009; Valdés-Ferrer et al, 2013; Deng et al, 2019; Wang J. et al, 2020). These findings suggest that HMGB1 could be a therapeutic target for preventing inflammation and ALI in sepsis
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