MI2026 – Prabhasha Jayasundara

Title:
Foam Cell Reprogramming, ER Stress Activation, and Lipid Metabolic Dysregulation in Alveolar Macrophages Exposed to Silica and Coal Dust

Abstract:
Occupational inhalation of respirable crystalline silica and coal dust is a fundamental cause of silicosis and coal workers’ pneumoconiosis (CWP). However, the cellular mechanisms behind disease progression are not fully understood. Alveolar macrophages (AMs) are the main mediators of particulate clearance, but how sustained particle burden affects macrophage lipid metabolism and stress signalling remains poorly characterised. This study uses an integrated metabolic and transcriptomic approach in a murine model of occupational lung disease (OLD) to clarify these mechanisms.

Dust-exposed mice showed increased airway hyperresponsiveness and signs of emphysematous and fibrotic remodelling compared to controls (p < 0.05). Raman microspectroscopy identified co-localisation of intracellular silica with lipid-rich cellular regions, indicating neutral lipid accumulation. Transcriptomic analysis of silica-positive AMs showed strong enrichment of foam cell–associated gene signatures. There was upregulation of scavenger and lipid uptake receptors, such as CD36, and suppression of reverse cholesterol transporters (ABCA1, ABCG1). Genes involved in fatty acid transport and β-oxidation were downregulated, suggesting impaired lipid catabolism. These lipid metabolic disturbances were linked to activation of ER stress pathways, implying lipid overload contributes to proteostatic dysfunction. Silica-negative AMs showed intermediate transcriptional changes. Coal dust–exposed AMs exhibited overlapping yet distinct metabolic reprogramming. Cross-dataset validation confirmed progressive, foam cell–like transcriptional remodelling with increasing particle burden over time. This study shows that particle-laden AMs exhibit coordinated lipid metabolic dysregulation, ER stress, and foam cell reprogramming. These are central processes in the pathogenesis of pneumoconiosis. Results suggest macrophage lipid homeostasis is a promising therapeutic target. Future research will define the temporal sequence of these events and test candidate interventions to slow early disease progression.

Biography:
I am Prabhasha Jayasundara, a PhD student in Immunology and Microbiology in Prof. Jay Horvat’s group at HMRI, The University of Newcastle, Australia. Originally from Sri Lanka, I hold a Bachelor’s degree in Chemical and Process Engineering from the University of Peradeniya. My research focuses on occupational lung diseases, particularly the impact of silica and coal dust exposure on alveolar macrophages, with an emphasis on lipid metabolism, foam cell formation, and ER stress pathways. I am also working on developing novel diagnostic approaches, including Raman-based detection methods, to monitor dust exposure and improve workplace safety.