School of Life Sciences, Ningxia University, Yinchuan 750021, China.
Key Laboratory of Ningxia Minority Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
Int J Mol Sci. 2023 Aug 11;24(16):12709. doi: 10.3390/ijms241612709.
Pyroptosis is a host immune strategy to defend against (Mtb) infection. , a calcium-binding protein that plays an important role in promoting cancer progression as well as the pathophysiological development of various non-tumor diseases, has not been explored in Mtb-infected hosts. In this study, transcriptome analysis of the peripheral blood of patients with pulmonary tuberculosis (PTB) revealed that and were significantly up-regulated in PTB patients' peripheral blood. Furthermore, there was a positive correlation between the expression of and . KEGG pathway enrichment analysis showed that differentially expressed genes between PTB patients and healthy controls were significantly related to inflammation, such as the NOD-like receptor signaling pathway and NF-κB signaling pathway. To investigate the regulatory effects of on macrophage pyroptosis, THP-1 macrophages infected with (BCG) were pre-treated with exogenous , inhibitor or si-. This research study has shown that promotes the pyroptosis of THP-1 macrophages caused by BCG infection and activates NLRP3 inflammasome and NF-κB signaling pathways, which can be inhibited by knockdown or inhibition of . In addition, inhibition of NF-κB or NLRP3 blocks the promotion effect of on BCG-induced pyroptosis of THP-1 macrophages. In conclusion, activates the NF-κB/NLRP3 inflammasome signaling pathway to promote macrophage pyroptosis induced by Mtb infection. These data provide new insights into how affects Mtb-induced macrophage pyroptosis.
细胞焦亡是宿主抵御结核分枝杆菌（Mtb）感染的一种免疫策略。Gasdermin D（GSDMD）是一种钙结合蛋白，在促进癌症进展以及各种非肿瘤疾病的病理生理发展中发挥重要作用，但在 Mtb 感染宿主中尚未得到探索。本研究通过对肺结核（PTB）患者外周血的转录组分析，发现 GSDMD 和 在 PTB 患者外周血中显著上调。此外，GSDMD 的表达与 呈正相关。KEGG 通路富集分析显示，PTB 患者和健康对照之间差异表达的基因与炎症显著相关，如 NOD 样受体信号通路和 NF-κB 信号通路。为了研究 GSDMD 对巨噬细胞焦亡的调控作用，用 （BCG）感染 THP-1 巨噬细胞，并用外源性 、 抑制剂或 si- 预处理。本研究表明，GSDMD 促进了 BCG 感染诱导的 THP-1 巨噬细胞的细胞焦亡，并激活了 NLRP3 炎性小体和 NF-κB 信号通路，可被敲低或抑制 所抑制。此外，抑制 NF-κB 或 NLRP3 可阻断 GSDMD 对 BCG 诱导的 THP-1 巨噬细胞焦亡的促进作用。综上所述，GSDMD 通过激活 NF-κB/NLRP3 炎性小体信号通路，促进 Mtb 感染诱导的巨噬细胞焦亡。这些数据为 GSDMD 如何影响 Mtb 诱导的巨噬细胞焦亡提供了新的见解。
