Transcriptomic profiling of host-pathogen interactions during early Mycobacterium tuberculosis infection stages
1 Department of Biological Sciences, Western Illinois University, USA.
2 Lagos State Ministry of Health (Grant Management Unit), Lagos, Nigeria.
Research Article
World Journal of Advanced Research and Reviews, 2024, 22(01), 2054–2073
Publication history:
Received on 24 February 2024; revised on 26 April 2024; accepted on 29 April 2024
Abstract:
Understanding the early molecular interactions between Mycobacterium tuberculosis (M.tb) and host immune cells is essential to identifying novel diagnostic markers and therapeutic targets for tuberculosis (TB). Despite advances in TB research, the global burden of the disease remains substantial, with millions of new infections annually, many in resource-constrained settings. The pathogen's ability to persist within host macrophages during initial infection stages underlies its pathogenicity and resistance to clearance. This study aims to elucidate transcriptomic changes in both host and pathogen during early stages of M.tb infection using high-throughput RNA sequencing (RNA-Seq). Human peripheral blood-derived macrophages were infected with virulent M.tb H37Rv, and dual RNA-Seq was performed at multiple early time points (2h, 6h, and 24h post-infection). Bioinformatic analysis revealed dynamic expression changes in host innate immune genes, including early upregulation of TNF, IL-6, and type I interferon pathways. Concurrently, M.tb exhibited transcriptional adaptation to intracellular stress, with induction of genes involved in dormancy survival, lipid metabolism, and ESX-1 secretion system. Gene ontology and KEGG pathway analyses indicated key host responses such as autophagy regulation, inflammasome activation, and metabolic reprogramming. Notably, a subset of non-coding RNAs and long intergenic transcripts were differentially expressed, suggesting novel regulatory mechanisms. These findings provide a comprehensive view of the early transcriptional landscape of M.tb-host interactions and offer candidate targets for host-directed therapies. Furthermore, transcriptomic biomarkers identified here hold promise for the development of early diagnostic tools to distinguish latent from active TB. Integration of transcriptomics with proteomics and epigenomics could enhance mechanistic understanding of TB pathogenesis.
Keywords:
Mycobacterium Tuberculosis; Transcriptomics; Host-Pathogen Interaction; Early Infection; Macrophages; RNA Sequencing
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Copyright © 2024 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0