Obesity is a major risk factor for infection and poor clinical outcomes, yet the mechanisms driving immune dysfunction in humans remain unclear. Sleep apnoea patients present with a wide BMI range, providing an ideal cohort to study obesity-related immune variation. Recently, cells of the innate immune system like monocytes and macrophages have emerged as susceptible to functional reprogramming due to various conditions, including obesity – termed trained immunity, a form of innate memory which can alter responses to infections and cancer. This reprogramming is brought about through epigenetic and metabolic changes in progenitor cells of the myeloid lineage.
This project will investigate whether BMI influences epigenetic and functional properties of patient-derived innate immune cells across a range of BMI, focusing on progenitor blood monocytes and their mature macrophage progeny. We hypothesize that obesity-associated chromatin modifications in blood monocytes correlate with impaired macrophage responses, contributing to heightened inflammation and reduced pathogen clearance.
I will isolate monocytes from blood samples collected at St. James Hospital and perform two assays: (1) flow cytometry-based detection of chromatin modifications linked to inflammatory states, and (2) functional assays on monocyte-derived macrophages, including measuring cytokine production after Toll-like receptor stimulation and assessing bacterial containment/phagocytosis.
By correlating chromatin signatures with functional outcomes across BMI categories, this work will establish a pipeline for profiling innate immune variability in humans. The project will provide me with hands-on training in clinical sample handling, flow cytometry, and cell-based assays while generating preliminary data for a future collaborative work between the groups and patients. Ultimately, while increasing awareness of immune vulnerability in patients, this research will advance understanding of how obesity impacts immune competence, informing strategies to improve clinical outcomes in obese populations.