Spatial and temporal transcriptomics of Schistosoma japonicum-induced hepatic granuloma formation reveals novel roles for neutrophils
Spatial and temporal transcriptomics of Schistosoma japonicum-induced hepatic granuloma formation reveals novel roles for neutrophils
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DOI：
10.1189/jlb.1212653
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发表时间：
2013-08-01
影响因子：
5.5
通讯作者：
Gobert, Geoffrey N.
中科院分区：
文献类型：
--
作者：
Chuah, Candy;Jones, Malcolm K.;Gobert, Geoffrey N.
中性粒细胞在介导日本血吸虫虫卵诱导的肝肉芽肿性病变的组织损伤和修复中的双重作用鸡胚卵块诱发的肝肉芽肿性病变的严重程度明显取决于宿主免疫反应的性质。在这项研究中，我们使用LMM和微阵列分析，比较基因表达谱的组织学不同的区域内，直接接近，肝肉芽肿，在C57 BL/6小鼠感染日本血吸虫。在肉芽肿核心（邻近虫卵）内，1型、2型和17型免疫相关基因显著上调，随后在肉芽肿外部区域2型和纤维化基因表达增加。中性粒细胞相关基因也被发现在感染后7周时在肉芽肿的核心和外周区差异表达，表明嗜中性粒细胞在S.日本血吸虫肉芽肿病理从感染小鼠肝脏获得的肉芽肿中显微镜下观察到NET的释放，并且当在S.日本虫卵这些发现首次提示中性粒细胞在介导链球菌组织损伤和修复中的双重作用。日本血吸虫虫卵诱导的肝肉芽肿性病变。总之，这些结果提供了肉芽肿微环境内发生的局部事件的概述。
A novel dual role for neutrophils in the mediation of tissue damage and repair in Schistosoma japonicum egg-induced hepatic granulomatous lesions. The severity of schistosome egg-induced hepatic granulomatous pathology depends markedly on the nature of the host immune responses. In this study, we used LMM and microarray analysis to compare gene expression profiles of histologically distinct zones within, and directly proximal to, hepatic granulomas that developed in C57BL/6 mice infected with Schistosoma japonicum. There was significant up-regulation of type-1, type-2, and type-17 immune-associated genes within the granuloma core (adjacent to eggs), followed by increased expression of type-2 and fibrotic genes at the outer zones of granulomas. Neutrophil-associated genes were also found to be expressed differentially in the core and at the peripheral zone of granulomas, present at 7 weeks p.i., demonstrating a significant role of neutrophils in S. japonicum granulomatous pathology. The release of NETs was observed microscopically in granulomas obtained from the livers of infected mice and when human neutrophils were incubated in vitro in the presence of S. japonicum eggs. These finding are the first to suggest a novel, dual role for neutrophils in the mediation of tissue damage and repair in S. japonicum egg-induced hepatic granulomatous lesions. Together, these results provide an overview of the local events occurring within the granuloma microenvironment.