Li Huihui, Qiu Dapeng, Yang Huijuan, Yuan Yuan, Wu Lingqin, Chu Liang, Zhan Bin, Wang Xiaoli, Sun Yan, Xu Wei, Yang Xiaodi
Department of Basic Medical College, Bengbu Medical College, Bengbu, China.
Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, China.
Front Cell Infect Microbiol. 2021 Mar 24;11:653843. doi: 10.3389/fcimb.2021.653843. eCollection 2021.
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 adult worms (-AES) on sepsis-induced ALI. In this study, the therapeutic efficacy of -AES on sepsis-induced ALI and the underlying immunological mechanism and the signaling pathway were investigated. The results indicated that after being treated with -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 -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 -AES. Our results demonstrated that -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 -AES through HMGB1/TLR2/MyD88 signal pathway. The findings suggest -AES is a potential therapeutic agent for prevention and treatment of sepsis-induced ALI and other inflammatory diseases.
急性肺损伤（ALI）是全身炎症或脓毒症的常见并发症，发病率和死亡率都很高。尽管许多研究已证实蠕虫衍生蛋白具有强大的免疫调节功能，可用于治疗炎症性疾病，但关于成虫排泄分泌产物（-AES）对脓毒症诱导的ALI的治疗效果尚无报道。在本研究中，我们研究了-AES对脓毒症诱导的ALI的治疗效果及其潜在的免疫机制和信号通路。结果表明，与所有小鼠均死亡的PBS对照组相比，用-AES治疗后，CLP诱导的脓毒症小鼠在CLP手术后72小时的存活率显著提高至50%。脓毒症诱导的ALI在很大程度上得到缓解，其特征为肺组织炎症细胞浸润和病理变化减少，肺损伤评分和肺湿/干重比降低。-AES的治疗效果与刺激Tregs反应有关，调节性细胞因子IL-10和TGF-β增加，促炎细胞因子（TNF-α、IL-6、IL-1β）下调。用-AES治疗后，肺组织中HMGB1、TLR2和MyD88的表达受到抑制。我们的结果表明，-AES在免疫调节中起重要作用，并通过抑制促炎细胞因子对脓毒症诱导的ALI具有治疗作用。Tregs的激活以及调节性细胞因子IL-10和TGF-β水平的增加可能通过HMGB1/TLR2/MyD88信号通路参与了-AES的免疫调节功能。这些发现表明，-AES是预防和治疗脓毒症诱导的ALI及其他炎症性疾病的潜在治疗药物。
