Necroptosis of Splenic Macrophages Induced by Streptococcus gallolyticus subsp pasteurianus
Necroptosis of Splenic Macrophages Induced by Streptococcus gallolyticus subsp pasteurianus
复制标题
溶没食子链球菌亚种诱导的脾巨噬细胞坏死性凋亡。
DOI：
10.1637/11449-061216-reg
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发表时间：
2017-03-01
期刊：
影响因子：
1.4
通讯作者：
Hu, Xueying
中科院分区：
文献类型：
--
作者：
Li, Meixia;Liu, Bo;Hu, Xueying
总结以前的研究表明，高毒力菌株的链球菌解没食子酸亚种。命名为AL 101002菌株的巴氏杆菌引起具有脾损伤的雏鸭的高死亡率。在本研究中，42只雏鸭皮下接种AL 101002菌株，以研究脾脏病变随时间的变化。接种后14天（dpi），这些雏鸭的脾脏因充血和水肿而显着扩大，和/或显示多个大理石花纹区域。从脾脏和血液中重新分离AL 101002菌株，并使用抗AL 101002抗体通过免疫组织化学（IHC）进行确认。组织学上，1 ~ 7 dpi脾脏主要病变为巨噬细胞坏死。末端dUTP缺口末端标记试验、透射电镜和抗巨唾液酸蛋白抗体（CD 68）的IHC证实巨噬细胞坏死为坏死性凋亡，并通过定量（实时）逆转录酶PCR分析进一步证实。细胞凋亡的两个主要因子，caspase 3和caspase 8，在AL 101002感染期间没有显著变化，表明细胞凋亡信号没有被激活。而关键因子混合系激酶样在感染后第1天至第14天显著升高（P < 0.05）。感染后第1天脾脏中炎症细胞因子IL-1β和IL-6的表达显著上调（P < 0.01）。肿瘤坏死因子α在dpi第1天至第5天下调，但在第7天至第14天升高。结果表明，AL 101002株主要感染巨噬细胞并导致巨噬细胞坏死性凋亡，提示脾脏巨噬细胞坏死性凋亡参与了S.解没食子酸亚种雏鸭的巴氏杆菌感染。
SUMMARY A previous study demonstrated that a highly virulent strain of Streptococcus gallolyticus subsp. pasteurianus, designated as the AL101002 strain, induced high mortality in ducklings with splenic lesions. In this study, 42 ducklings were subcutaneously inoculated with the AL101002 strain to study changes in splenic lesions over time. The spleens from these ducklings were significantly enlarged by congestion and edema, and/or showed multiple marbled areas 14 days postinoculation (dpi). The AL101002 strain was reisolated from the spleens and blood and confirmed by immunohistochemistry (IHC) with the use of anti-AL101002 antibody. Histopathologically, the main lesion was macrophage necrosis in the spleens from 1 to 7 dpi. Terminal dUTP nick-end labeling assay, transmission electron microscopy, and IHC by anti-macrosialin antibody (CD68) demonstrated that macrophage necrosis was necroptosis, which was further confirmed by quantitative (real-time) reverse-transcriptase PCR analysis. Two major factors of apoptosis, caspase 3 and caspase 8, did not significantly change during the AL101002 infection, suggesting that apoptosis signals were not activated. However, the key factor mixed lineage kinase like was increased significantly (P < 0.05) from Day 1 to Day 14 dpi. Inflammatory cytokine interleukin-1β and interleukin-6 had significantly (P < 0.01) upregulated expression in the spleens on Day 1 dpi. Tumor necrosis factor α was downregulated from Day 1 to Day 5 dpi, but increased from Day 7 to Day 14. Our results demonstrated that AL101002 strain mainly infects macrophages and resulted in macrophage necroptosis and suggested that macrophage necroptosis in spleens is involved in the pathogenesis of S. gallolyticus subsp. pasteurianus infection in ducklings.