Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United States.
Front Immunol. 2020 Jun 11;11:1174. doi: 10.3389/fimmu.2020.01174. eCollection 2020.
Helminths are masters at modulating the host immune response through a wide variety of versatile mechanisms. These complex strategies facilitate parasite survival in the host and can also be exploited to prevent chronic immune disorders by minimizing excessive inflammation. Extracellular vesicles (EVs) are small membrane-bound structures secreted by helminths which mediate immune evasion during parasite infection. The goal of this study was to investigate the immunoregulatory properties of EVs (-EVs) in a murine model of colitis. We found that -EVs significantly ameliorated 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. -EVs alleviated intestinal epithelium barrier damage, markedly reduced pro-inflammatory cytokine secretion and neutrophil infiltration, and upregulated immunoregulatory cytokine expression in colon tissue. -EVs also modulated the adaptive immune response by influencing T-cell composition. The numbers of Th1 and Th17 cells in MLNs, as well as the expression levels of Th1/Th17-associated cytokines and transcription factors in colon were reduced. In contrast, Th2 and Treg cells were increased after -EVs treatment. Furthermore, sequencing of EV-derived microRNAs (miRNAs) indicated that an array of miRNAs was involved in the regulation of the host immune response, including inflammation. These findings expand our knowledge of host-parasite interactions, and may help design novel and effective strategies to prevent parasite infections or to treat inflammatory diseases like IBD. Further studies are needed to identify the specific cargo molecules carried by -EVs and to clarify their roles during infection.
寄生虫通过多种多功能机制巧妙地调节宿主的免疫反应。这些复杂的策略有助于寄生虫在宿主体内的生存，并且还可以通过最小化过度炎症来防止慢性免疫紊乱。细胞外囊泡 (EVs) 是寄生虫感染期间介导免疫逃避的寄生虫分泌的小的膜结合结构。本研究的目的是研究 EVs（-EVs）在结肠炎小鼠模型中的免疫调节特性。我们发现 -EVs 可显著改善 2,4,6-三硝基苯磺酸 (TNBS) 诱导的结肠炎小鼠的症状。-EVs 减轻了肠道上皮屏障损伤，显著减少了促炎细胞因子的分泌和中性粒细胞浸润，并上调了结肠组织中免疫调节细胞因子的表达。-EVs 还通过影响 T 细胞组成来调节适应性免疫反应。肠系膜淋巴结 (MLN) 中的 Th1 和 Th17 细胞数量以及结肠中 Th1/Th17 相关细胞因子和转录因子的表达水平降低。相比之下，-EVs 治疗后 Th2 和 Treg 细胞增加。此外，EV 衍生 microRNAs (miRNAs) 的测序表明，一系列 miRNAs 参与了宿主免疫反应的调节，包括炎症。这些发现扩展了我们对宿主-寄生虫相互作用的认识，并可能有助于设计预防寄生虫感染或治疗炎症性疾病（如 IBD）的新的有效策略。需要进一步研究以确定 -EVs 携带的特定载体分子，并阐明它们在感染过程中的作用。
