Zhou Hongli, Chen Zhe, Limpanont Yanin, Hu Yue, Ma Yubin, Huang Ping, Dekumyoy Paron, Zhou Minyu, Cheng Yixin, Lv Zhiyue
Joint Program of Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
Front Microbiol. 2020 Jan 23;10:3126. doi: 10.3389/fmicb.2019.03126. eCollection 2019.
Infection with the roundworm is the main cause of eosinophilic meningitis worldwide. The underlying molecular basis of the various pathological outcomes in permissive and non-permissive hosts infected with remains poorly defined. In the present study, the histology of neurological disorders in the central nervous system (CNS) of infected rats was assessed by using hematoxylin and eosin staining. Quantitative reverse transcription polymerase chain reaction (RT-qPCR), western blot and immunofluorescence (IF) were used in evolutions of the transcription and translation levels of the apoptosis-, necroptosis-, autophagy-, and pyroptosis-related genes. The distribution of apoptotic and necroptotic cells in the rat hippocampus and parenchyma was further detected using flow cytometry, and the features of the ultrastructure of the cells were examined by transmission electron microscopy (TEM). The inflammatory response upon CNS infection with evolved, as characterized by the accumulation of a small number of inflammatory cells under the thickened meninges, which peaked at 21 days post-infection (dpi) and returned to normal by 35 dpi. The transcription levels and translation of and increased significantly at 21 and 28 dpi but decreased sharply at 35 dpi compared to those in the normal control group. However, the changes in the expression of caspase-1, caspase-3, caspase-11, Beclin-1 and LC3B were not obvious, suggesting that apoptosis and necroptosis but not autophagy or pyroptosis occurred in the brains of infected animals at 21 and 28 dpi. The results of RT-qPCR, western blot analysis, IF, flow cytometry and TEM further illustrated that necroptosis and caspase-2-mediated apoptosis occurred in astrocytes and neurons but not in microglia in the parenchyma and hippocampus of infected animals. This study provides the first evidence that neuronal and astrocytic necroptosis and -mediated apoptosis are induced by infection in the parenchymal and hippocampal regions of rats at 21 and 28 dpi but these processes are negligible at 35 dpi. These findings enhance our understanding of the pathogenesis of . infection and provide new insights into therapeutic approaches targeting the occurrence of cell death in astrocytes and neurons in infected patients.
蛔虫感染是全球嗜酸性粒细胞性脑膜炎的主要病因。在感染了[蛔虫名称未给出]的允许性和非允许性宿主中，各种病理结果的潜在分子基础仍不清楚。在本研究中，通过苏木精和伊红染色评估感染大鼠中枢神经系统（CNS）中神经疾病的组织学。定量逆转录聚合酶链反应（RT-qPCR）、蛋白质免疫印迹和免疫荧光（IF）用于评估凋亡、坏死性凋亡、自噬和焦亡相关基因的转录和翻译水平。使用流式细胞术进一步检测大鼠海马和实质中凋亡和坏死性凋亡细胞的分布，并通过透射电子显微镜（TEM）检查细胞超微结构的特征。感染[蛔虫名称未给出]后中枢神经系统的炎症反应逐渐发展，其特征是增厚的脑膜下有少量炎症细胞积聚，在感染后21天（dpi）达到峰值，并在35 dpi恢复正常。与正常对照组相比，[相关基因名称未给出]的转录水平和翻译在21和28 dpi时显著增加，但在35 dpi时急剧下降。然而，半胱天冬酶-1、半胱天冬酶-3、半胱天冬酶-11、贝林蛋白-1和微管相关蛋白轻链3B（LC3B）表达的变化不明显，表明在感染动物的大脑中，在21和28 dpi时发生了凋亡和坏死性凋亡，但没有自噬或焦亡。RT-qPCR、蛋白质免疫印迹分析、IF、流式细胞术和TEM的结果进一步表明，在感染动物的实质和海马中，坏死性凋亡和半胱天冬酶-2介导的凋亡发生在星形胶质细胞和神经元中，而不是小胶质细胞中。本研究首次证明，在21和28 dpi时，大鼠实质和海马区域的[蛔虫名称未给出]感染可诱导神经元和星形胶质细胞坏死性凋亡以及[相关名称未给出]介导的凋亡，但在35 dpi时这些过程可忽略不计。这些发现加深了我们对[蛔虫名称未给出]感染发病机制的理解，并为针对感染患者星形胶质细胞和神经元中细胞死亡发生的治疗方法提供了新的见解。
