结核分枝杆菌菌株基因型和耐药状态在A549肺上皮细胞系凋亡细胞死亡和炎症通路基因表达中的意义。
Significance of genotypes and resistance status of Mycobacterium tuberculosis strains in gene expression of apoptosis cell death and inflammatory pathways in A549 lung epithelial cell line.
发表日期:2024
作者:
Rouhollah Abdolhamidi, Setareh Haghighat, Arfa Moshiri, Abolfazl Fateh, Seyed Davar Siadat
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
纵观历史,结核病(TB)一直是一个主要的健康问题。作为结核病感染的一部分,宿主与结核分枝杆菌 (Mtb) 的相互作用非常重要。通过免疫病理学和细胞死亡控制过程,结核分枝杆菌感染促进细胞内生长。 Mtb 感染中细胞凋亡与炎症之间的关系仍不清楚。本研究评估了感染多种Mtb菌株的A549细胞中相关凋亡和炎症基因的水平。不同表型(敏感、INHR、RifR、MDR和XDR)的Mtb分离株收集自伊朗巴斯德研究所,在本研究期间。之前对所有菌株进行了全基因组测序,并选择北京基因型为敏感。此外,对于其他抗性菌株,New-1 基因型可用并分离用于基因型比较。 A549 肺癌细胞也被培养并用选定的 Mtb 菌株感染。采用逆转录聚合酶链反应(RT-PCR)检测涉及炎症和凋亡的基因。发现所有敏感菌株和耐药菌株均显着上调抗凋亡因子(bcl2和rb1)、趋化因子(IL-8和MCP-1) )和促炎细胞因子(TNF-α 和 IFN-γ)表达,而感染 24 小时和 48 小时后,观察到抗炎基因(IL-10)和促凋亡基因(坏基因和促凋亡基因)显着下调。巴克斯)。除了抗性菌株外,结核分枝杆菌基因型也影响基因表达。北京基因型(敏感分离株)比 New-1 基因型(INHR、RifR、MDR 和 XDR)对炎症和凋亡基因的影响更大。本研究中检测的与凋亡和炎症相关的基因表达差异可能归因于基因型,而不是基因型。与敏感菌株(北京基因型)相比,大多数基因的表达在耐药菌株(属于New-1基因型的INHR、RifR、MDR和XDR)中被观察到较低,因此大多数基因的表达较低。
Tuberculosis (TB) has been a major health issue throughout history. As part of TB infection, host-Mycobacterium tuberculosis (Mtb) interactions are important. Through immune pathology and cell death control processes, Mtb infection facilitates intracellular growth. The relationship between apoptosis and inflammation in Mtb infection remains unclear. In this study, the levels of related apoptosis and inflammatory genes were assessed in A549 cells infected with a variety of Mtb strains.Mtb isolates with different phenotypes (sensitive, INHR, RifR, MDR, and XDR) were collected from the Pasteur Institute of Iran, during this study. Whole genome sequencing was previously performed on all strains, and the Beijing genotype was selected as sensitive. Also, for other resistant strains, the New-1 genotype was available and isolated for genotype comparison. A549 lung carcinoma cells were also grown and infected with selected Mtb strains. Genes involved in inflammation and apoptosis were detected using reverse transcription-PCR (RT-PCR).All sensitive strains and resistant strains were found to significantly up-regulate anti-apoptotic (bcl2 and rb1), chemokine (IL-8 and MCP-1), and pro-inflammatory cytokine (TNF-α and IFN-γ) expression, while significant down-regulation was observed after 24 and 48 hr of infection in anti-inflammatory genes (IL-10) and pro-apoptotic genes (bad and bax). Besides resistance strains, Mtb genotypes also affected gene expression. The Beijing genotype (sensitive isolate) influences inflammatory and apoptotic genes more sharply than the New-1 genotype (INHR, RifR, MDR, and XDR).Gene expression differences related to apoptosis and inflammation examined in the current study may be attributed to genotypes rather than resistance status since the expression of most genes has been observed to be lower in resistant strains (INHR, RifR, MDR, and XDR belonging to the New-1 genotype) compared to sensitive strains (Beijing genotype).