Overview
Tuberculosis develops in only a fraction of people exposed to Mycobacterium tuberculosis, while others clear the bacteria before infection takes hold. The reasons for these different outcomes remain unclear. Our research investigates how lung macrophage responses, shaped by their epigenetic state and gene expression programs, regulate whether infection is controlled or sustained.
Our contribution
Using human lung macrophages and advanced single-cell technologies, we identified distinct macrophage clusters with specialized immune programs. One of these clusters is enriched for inflammatory and antimicrobial pathways. Our findings show that individuals with a higher proportion of specific cluster macrophages exhibit better control of bacterial growth, suggesting this cluster may be a key determinant of infection outcomes.
Current focus
-Defining the antimicrobial functions of specific lung macrophage clusters using infection assays, flow cytometry, and gene editing.
-Testing whether specific lung macrophage clusters correlate with sustained infection in people recently exposed to tuberculosis.
-Developing predictive models that could help identify who is at the highest risk of establishing infection.
Impact
This project will reveal how human macrophage heterogeneity shapes early infection control, leading to new biomarkers and therapeutic strategies for tuberculosis prevention and treatment.