Angiostrongylus cantonensis infection is a major cause of eosinophilic meningitis (EM). Severe cases or cases that involve infants and children present poor prognoses. MicroRNAs (miRNAs), which are important regulators of gene expression in many biological processes, were recently found to be regulators of the host response to infection by parasites; however, their roles in brain inflammation caused by A. cantonensis are still unclear. The current study confirmed that miR-155-5p peaked at 21 days after A. cantonensis infection, and its expression was positively correlated with the concentration of excretory and secretory products (ESPs). We found that miR-155-5p knockdown lentivirus successfully ameliorated brain injury and downregulated the expression of major basic protein (MBP) in vivo, and the number of eosinophils in CSF (and the percentage of eosinophils in peripheral blood were also decreased in the miR-155-5p knockdown group. Moreover, the expression of several eosinophilic inflammation cytokines such as CCL6/C10, ICAM-1, and MMP9, declined after the miR-155-5p knockdown. SOCS1 protein, which is an important negative regulator of inflammation activation, was identified as a direct miR-155-5p target. We further detected the effect of miR-155-5p knockdown on phosphorylated-STAT3 and phosphorylated-p65 proteins, which were found to be negatively regulated by SOCS1 and play an important role in regulating the inflammatory response. We found that miR-155-5p knockdown decreased the activity of p-STAT3 and p-p65, thereby leading to lower expression of MMP9 and TSLP proteins, which were closely related to the chemotaxis and infiltration of eosinophils. Interestingly, the inhibition of p-STAT3 or p-p65 was found to induce the downregulation of miR-155-5p in an opposite manner. These observations suggest that a positive feedback loop was formed between miR-155-5p, STAT3, and NF-κB in A. cantonensis infection and that miR-155-5p inhibition might provide a novel strategy to attenuate eosinophilic meningitis.

广州管圆线虫感染是嗜酸性粒细胞性脑膜炎 (EM) 的主要原因。严重病例或涉及婴儿和儿童的病例预后不佳。MicroRNAs (miRNAs) 是许多生物过程中基因表达的重要调节因子，最近被发现是宿主对寄生虫感染反应的调节因子。然而，它们在A. cantonensis引起的脑部炎症中的作用仍不清楚。目前的研究证实，miR-155-5p在广州曲霉后21天达到峰值感染，其表达与排泄和分泌产物（ESP）的浓度呈正相关。我们发现miR-155-5p敲低慢病毒在体内成功改善脑损伤并下调主要碱性蛋白（MBP）的表达，CSF中嗜酸性粒细胞的数量（以及外周血中嗜酸性粒细胞的百分比也在miR中降低） -155-5p 敲低组。此外，CCL6/C10、ICAM-1 和 MMP9 等几种嗜酸性炎症细胞因子的表达在 miR-155-5p 敲低后下降。SOCS1 蛋白是炎症的重要负调节因子激活，被确定为一个直接的 miR-155-5p 目标。我们进一步检测了 miR-155-5p 敲低对磷酸化-STAT3 和磷酸化-p65 蛋白的影响，被发现受 SOCS1 负调控并在调节炎症反应中起重要作用。我们发现 miR-155-5p 敲低会降低 p-STAT3 和 p-p65 的活性，从而导致 MMP9 和 TSLP 蛋白的表达降低，这与嗜酸性粒细胞的趋化性和浸润密切相关。有趣的是，发现 p-STAT3 或 p-p65 的抑制以相反的方式诱导 miR-155-5p 的下调。这些观察结果表明，在 miR-155-5p、STAT3 和 NF-κB 之间形成了正反馈回路。与嗜酸性粒细胞的趋化和浸润密切相关。有趣的是，发现 p-STAT3 或 p-p65 的抑制以相反的方式诱导 miR-155-5p 的下调。这些观察结果表明，在 miR-155-5p、STAT3 和 NF-κB 之间形成了正反馈回路。与嗜酸性粒细胞的趋化和浸润密切相关。有趣的是，发现 p-STAT3 或 p-p65 的抑制以相反的方式诱导 miR-155-5p 的下调。这些观察结果表明，在 miR-155-5p、STAT3 和 NF-κB 之间形成了正反馈回路。A. cantonensis感染和 miR-155-5p 抑制可能提供一种减轻嗜酸性脑膜炎的新策略。