The relationship between innate immune cell function and bacterial infections in severe acute malnutrition (360G-Wellcome-206225_Z_17_Z)

Severe acute malnutrition (SAM) underlies one million deaths in children under 5 years old annually. Immunodeficiency is implicated in SAM mortality because deaths are predominantly due to infections and infectious mortality persists after nutritional rehabilitation; however, we know very little about how malnutrition affects immune cell function. This fellowship will characterise the relationship between bacterial infections and the anti-bacterial functions of monocytes and dendritic cells (DC) using blood samples collected from children admitted to hospital with SAM (n=200) and track this relationship during hospitalisation and over 48 weeks of community-based nutritional rehabilitation (n=100). I will evaluate both the capacity of monocytes and DC to bind and respond to bacteria in vitro, and how pro-inflammatory mediators in plasma, which are elevated in SAM, affect healthy monocyte and DC. These assays will generate a detailed profile of monocyte and DC function in each child which I will use to determine whether innate immune function is: 1) compromised relative to adequately-nourished controls (n=200); 2) associated with bacterial morbidity and mortality; and, 3) restored by treatment. Understanding the relationship between innate immune cell dysfunction and bacterial mortality in children with SAM could identify new immunotherapeutic targets to improve clinical outcomes in this high-risk population.