结核病中的酸性微环境通过调节巨细胞的炎症反应,增加了细胞外基质的降解
Ashley M Whittington1, Frances S Turner2, Friedrich Baark1
1Department of Infectious Disease, Imperial College London, London, United Kingdom.
PLoS pathogens
|July 7, 2023
概括
结核病 (TB) 感染的酸性环境会损害免疫反应,并增加对肺部有害的基质降解. 向酸性酶受体可能为结核病患者提供新的宿主导疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 病理学 病理学 病理学
背景情况:
- 结核菌菌菌 (M.tb) 感染导致严重的肺炎和破坏.
- 已知M.tb感染期间的酸性细胞外环境,但其对免疫反应的影响尚不清楚.
研究的目的:
- 为了研究酸性病对M.tb感染的免疫反应的影响.
- 确定将酸性结核与M.tb诱导的肺病理联系起来的分子机制.
主要方法:
- 对感染M.tb的人类巨细胞的RNA测序 (RNA-seq) 分析.
- 细胞模型用于评估矩阵金属蛋白酶 (MMP) 分泌.
- 用小鼠模型和患者样本研究酸性酶信号受体 (OGR-1,TDAG-8).
主要成果:
- 酸化诱导了巨细胞的广泛转录变化,对细胞外基质 (ECM) 降解途径和MMPs进行上调调节.
- 酸化抑制了关键的免疫细胞因子 (TNF-α,IFN-γ) 和增加了MMP-1和-3分泌.
- 酸化受体OGR-1和TDAG-8在M.tb感染的组织和结核淋巴腺炎患者中表达,调解了pH依赖的免疫效应.
结论:
- 结核病中的酸性微环境抑制了保护性免疫力,并促进了ECM的降解,导致肺部的破坏.
- 酸化受体代表了结核病宿主导治疗的潜在治疗点.
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