Alveolar macrophage transcriptional signatures associated with resistance to TST/IGRA conversion following Mycobacterium tuberculosis exposure.

Alveolar macrophage transcriptional signatures associated with resistance to TST/IGRA conversion following Mycobacterium tuberculosis exposure.

Publication date: Oct 31, 2025

Despite heavy exposure to Mycobacterium tuberculosis (Mtb), some individuals are resistant to TST and IGRA conversion (RSTRs). The functional and immunological mechanisms governing resistance are poorly understood. We hypothesized that RSTR and LTBI alveolar macrophages (AMs) respond differently to Mtb infection with transcriptional programs that are distinct from peripheral blood monocytes. We examined media and Mtb-infected AMs from bronchoalveolar lavage fluid collected from a RSTR cohort in Uganda with over 10 years of clinical follow-up. With transcriptional profiles of BAL cells analyzed immediately after collection, gene set enrichment analysis (GSEA) revealed 13 differentially expressed gene sets between RSTR (n = 19) and LTBI (n = 26) groups, including one (Hallmark E2F targets) which was positively enriched in the RSTR group (FDR 

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Concepts Keywords
Bronchoalveolar Adult
Enriched Alveolar macrophages
Mycobacterium Disease Resistance
Tuberculosis Female
Uganda Gene Expression Profiling
Humans
Latent Tuberculosis
Macrophages, Alveolar
Male
Mycobacterium tuberculosis
Resisters
Transcriptome
Transcriptome
Tuberculosis

Semantics

Type Source Name
disease MESH infection
disease IDO blood
drug DRUGBANK Dimercaprol
pathway REACTOME Reproduction
drug DRUGBANK Coenzyme M
disease MESH Latent Tuberculosis
disease MESH Tuberculosis
pathway KEGG Tuberculosis

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