Naomi Daniels Poster 2025

Dr Naomi Daniels

University of Otago, New Zealand

Immune Evasion Strategies of Beijing-Genotype Mycobacterium tuberculosis: Insights from Spatial Transcriptomic Analysis

Poster Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis, with over 10 million cases and 1.6 million deaths annually. Lineage 2-Beijing Mtb strains, predominant in East Asia, present a major challenge due to hypervirulence, multidrug resistance, and high relapse rates. Alarmingly, the Bacillus Calmette–Guérin (BCG) vaccine provides limited protection against Beijing strains, as seen in case-contact studies and murine models.

Our research investigates Beijing Mtb’s immune evasion strategies to inform next-generation TB vaccines. Using an aerosol infection model with fluorescently tagged clinical strains of Beijing- and Lineage 4-Mtb, we performed spatial transcriptomic analyses to profile immune responses in lung tissue and an in vitro macrophage growth inhibition assay (MGIA) to assess functional differences in alveolar macrophages.

Spatial transcriptomics revealed distinct immune cell co-localisation patterns in Beijing- versus L4-Mtb-infected lungs. Differentially expressed gene (DEG) analysis showed that Beijing Mtb suppresses critical host defence pathways, downregulating genes involved in trained immunity, phagocytosis, and antigen presentation, while upregulating immune evasion genes. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis highlighted suppression of pathways essential for TB immunity, including Toll-like receptor (TLR) signalling, antigen presentation, and T cell differentiation. Beijing Mtb also altered metabolic pathways, such as oxidative phosphorylation and glycolysis, potentially impairing immune function.

Cell-cell communication analyses suggested mechanisms by which Beijing Mtb may evade intracellular killing by disrupting macrophage antimicrobial pathways, supported by MGIA results showing significantly higher bacterial burden in Beijing Mtb-infected macrophages.

In summary, Beijing Mtb employs multifaceted immune evasion strategies, impairing trained immunity, macrophage bactericidal function, and metabolic reprogramming. These insights may contribute to the rational design of improved TB vaccines capable of targeting hypervirulent Mtb strains, such as the Beijing genotype, addressing a critical gap in TB prevention strategies.

Biography

Naomi completed her PhD at the Malaghan Institute of Medical Research, Wellington, New Zealand. Presently a Postdoctoral Research Fellow at the University of Otago in Dunedin, New Zealand, Naomi's research centres on unraveling the mechanisms employed by highly virulent strains of Mycobacterium tuberculosis to evade protective immunity induced by the BCG vaccine. This work aims to contribute to the rational design of improved TB vaccines capable of targeting hypervirulent Mtb strains, such as the Beijing genotype, addressing a critical gap in TB prevention strategies.