Toxoplasma gondii Infection Induces High Mobility Group Box 1 Released from Mouse Macrophages.
Toxoplasma gondii Infection Induces High Mobility Group Box 1 Released from Mouse Macrophages.
复制标题
弓形虫感染诱导小鼠巨噬细胞释放高迁移率 Group Box 1
DOI：
10.3389/fmicb.2017.00658
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发表时间：
2017
影响因子：
5.2
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Wang H;Li M;Liu J;Xu J;Han Q;Liu Q
高迁移率族蛋白1(HMGB1)广泛表达于细胞内参与的DNA结合能力。然而，更重要的是，在释放到细胞外时，它是通过促炎反应和免疫调节来对抗感染的武器。弓形虫引起炎性病理改变，包括慢性感染中的回肠炎和脑炎。为了研究HMGB1是否与弓形虫病的病变有关，我们检测了HMGB1在弓形虫感染过程中的变化。结果表明，感染弓形虫的小鼠巨噬细胞株ANA1和小鼠腹膜巨噬细胞(PMΦS)HMGB1转录下调，而经干扰素-γ处理的巨噬细胞和感染弓形虫小鼠的腹膜渗出液细胞HMGB1转录上调。细胞内HMGB1含量与ANA1转录水平基本一致，而小鼠PMΦS细胞内HMGB1含量无明显变化，ANA1和小鼠PMΦS感染寄生虫后均释放HMGB1，与干扰素-γ治疗组相比，胞浆内未见明显的HMGB1聚集。此外，我们还证实了弓形虫入侵导致HMGB1的释放，这种释放依赖于Caspase 1的活性。这些发现将有助于进一步研究细胞外HMGB1在弓形虫病中的作用。
High mobility group box 1 (HMGB1) is abundantly expressed in intracellular engaged DNA binding ability. However, more importantly, it is a weapon against infection through proinflammatory response and immune regulation while released to extracellular. Toxoplasma gondii causes inflammatory pathological changes including ileitis and encephalitis in chronic infection. To investigate whether HMGB1 contributes to the toxoplasmosis lesions, we examined HMGB1 changes during T. gondii infection. The results showed that HMGB1 transcription was down-regulated in the murine macrophage ANA1 cell line and mouse peritoneal macrophages (PMΦs) after T. gondii inoculation, but up-regulated in the IFN-γ treated macrophages and the intraperitoneal exudate cells from the T. gondii infected mice. The content of intracellular HMGB1 are basically consistent with the transcription levels in ANA1 assay, while there were no obvious changes in the mouse PMΦs. Both ANA1 and mouse PMΦs released HMGB1 after parasites infection, and no obvious HMGB1 aggregation in cytoplasm compare to the IFN-γ treatment group. Furthermore, we demonstrated that T. gondii invasion led to HMGB1 release, which was dependent on the Caspase 1 activity. These finding should promote to further investigate the functions of extracellular HMGB1 in the toxoplasmosis.