1- Department of Microbiology, TeMS.C.,Islamic Azad University, Tehran, Iran 2- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
Abstract: (7 Views)
Background: Tuberculosis has long been a significant challenge to global healthcare. The host-pathogen interaction with Mycobacterium tuberculosis plays a critical role in the progression of the infection, influencing immune responses and regulating cell death processes such as apoptosis and necrosis. However, the relationship between these processes and inflammation remains unclear. This study examines the expression levels of genes related to apoptosis, necrosis, and inflammation in A549 lung epithelial cells infected with drug-sensitive and drug-resistant Mycobacterium tuberculosis strains. Materials and methods: Strains of Mycobacterium tuberculosis with varying antibiotic resistance (sensitive, rifampin-resistant, multidrug-resistant, and extensively drug-resistant) were obtained from the Pasteur Institute of Iran. A549 cells were cultured and infected. Genes linked to the studied pathways were selected using bioinformatics, and their expression levels were assessed using RT-PCR. Results: All strains showed increased expression of anti-apoptotic genes (BCL2, RB1), chemokines (IL8, MCP1), and pro-inflammatory cytokines (TNF-α, IFN-γ), alongside reduced expression of anti-inflammatory genes (IL10) and pro-apoptotic genes (BAD, BAX) post-infection. The Beijing genotype (sensitive strain) induced higher inflammatory and apoptotic gene expression than the New-1 genotype (resistant strains). No significant changes were observed in necrosis-related genes (FADD, RIPK1). Conclusion: Variations in apoptosis and inflammation-related gene expression appear to stem more from genotypic differences than drug resistance. This underscores the pivotal role of the Mycobacterium tuberculosis genotype in modulating host immune responses during infection.
Abdolhamidi R, Haghighat S, Moshiri A, Fateh A, Siadat S D. Investigation of the impact of drug-sensitive and drug-resistant Mycobacterium tuberculosis Strains on inflammatory pathways and cell death in A549 lung epithelial cells. MEDICAL SCIENCES 2025; 35 (4) :436-449 URL: http://tmuj.iautmu.ac.ir/article-1-2333-en.html