Department of Immunology, Binzhou Medical University, Yantai, Shandong, P. R. China.
National Institute of Parasitic Diseases, Chinese Centre for Disease Control and Prevention, WHO Collaborating Centre for Tropical Diseases, National Centre for International Research on Tropical Diseases, Key Laboratory of Parasite and Vector Biology of the Chinese Ministry of Health, Shanghai, China.
PLoS Negl Trop Dis. 2023 Oct 3;17(10):e0011625. doi: 10.1371/journal.pntd.0011625. eCollection 2023 Oct.
Excretory/secretory products (ESPs) derived from helminths have been reported to effectively control allergic inflammation, which have better therapeutic prospects than live parasite infections. However, it remains unknown whether ESPs from schistosome eggs can protect against allergies, despite reports alleging that schistosome infection could alleviate disordered allergic inflammation.
In the present study, we investigated the protective effects of ESPs from Schistosoma japonicum eggs (ESP-SJE) on asthmatic inflammation. Firstly, we successfully established an allergic airway inflammation model in mice by alum-adjuvanted ovalbumin (OVA) sensitization and challenge. ESP-SJE were administered intraperitoneally on days -1 and 13 (before sensitization), on day 20 (before challenge), and on days 21-24 (challenge phase).
The results showed that ESP-SJE treatment significantly reduced the infiltration of inflammatory cells, especially eosinophils into the lung tissue, inhibited the production of the total and OVA-specific IgE during OVA-sensitized and -challenged phases, respectively, and suppressed the secretion of Th2-type inflammatory cytokines (IL-4). Additionally, ESP-SJE treatment significantly upregulated the regulatory T cells (Tregs) in the lung tissue during OVA challenge. Furthermore, using liquid chromatography-mass spectrometry analysis and Treg induction experiments in vitro, we might identify nine potential therapeutic proteins against allergic inflammation in ESP-SJE. The targets of these candidate proteins included glutathione S-transferase, egg protein CP422 precursor, tubulin alpha-2/alpha-4 chain, actin-2, T-complex protein 1 subunit beta, histone H₄, whey acidic protein core region, and molecular chaperone HtpG.
Taken together, the results discussed herein demonstrated that ESP-SJE could significantly alleviate OVA-induced asthmatic inflammation in a murine model, which might be mediated by the upregulation of Treg in lung tissues that may be induced by the potential modulatory proteins. Therefore, potential proteins in ESP-SJE might be the best candidates to be tested for therapeutic application of asthma, thus pointing out to a possible new therapy for allergic airway inflammation.
寄生虫的排泄/分泌产物(ESP)已被报道能有效控制过敏炎症,其治疗前景优于寄生虫活感染。然而,尽管有报道称血吸虫感染可以缓解紊乱的过敏炎症,但仍不清楚来自血吸虫卵的 ESP 是否可以预防过敏。
本研究通过卵清白蛋白(OVA)致敏和激发建立哮喘气道炎症模型,探讨日本血吸虫卵 ESP(ESP-SJE)对哮喘炎症的保护作用。首先,ESP-SJE 于致敏前 1 天和 13 天(-1 和 13 天)、激发前 20 天(20 天)、激发阶段(21-24 天)腹腔注射给药。
结果表明,ESP-SJE 治疗显著减少了炎症细胞浸润,特别是嗜酸性粒细胞浸润到肺组织,抑制了 OVA 致敏和激发阶段总 IgE 和 OVA 特异性 IgE 的产生,抑制了 Th2 型炎症细胞因子(IL-4)的分泌。此外,ESP-SJE 治疗在 OVA 激发阶段显著上调了肺组织中的调节性 T 细胞(Treg)。此外,通过液质联用分析和体外 Treg 诱导实验,我们可能在 ESP-SJE 中鉴定出 9 种针对过敏炎症的潜在治疗蛋白。这些候选蛋白的靶标包括谷胱甘肽 S-转移酶、卵蛋白 CP422 前体、微管蛋白 α-2/α-4 链、肌动蛋白-2、T 复合物蛋白 1 亚基 β、组蛋白 H4、乳清酸性蛋白核心区和分子伴侣 HtpG。
综上所述,本研究结果表明,ESP-SJE 可显著减轻小鼠模型 OVA 诱导的哮喘炎症,可能是通过上调肺组织中的 Treg 介导的,肺组织中的 Treg 可能是由潜在的调节蛋白诱导的。因此,ESP-SJE 中的潜在蛋白可能是治疗哮喘的最佳候选蛋白,为过敏性气道炎症的治疗提供了新的可能。