The relationship between innate immune cell function and bacterial infections in severe acute malnutrition

Severe acute malnutrition (SAM) underlies one million deaths in children under five years old annually. SAM is identified by extreme weight loss, but deaths are predominantly due to infection, particularly with bacteria. The immune system is critical for controlling infections, but we know very little about how immune cells function in people who are malnourished.

I will characterise the relationship between bacterial infections and the anti-bacterial functions of two innate immune cell types – monocytes and dendritic cells (DC) – using blood samples collected from children hospitalised with SAM, and track this relationship during hospitalisation and over 48 weeks post-discharge. I will culture blood with bacterial components to determine how well monocytes and DCs bind to and become activated by bacteria, which are indicators of their capacity to control infection. I will also characterise how healthy monocytes and DC change when exposed to blood from children with SAM. I aim to determine whether monocyte and DC function are compromised when compared with adequately-nourished controls and if they are associated with death and illness due to bacterial infections; and are restored by treatment.

Understanding which defects in innate immune cell function contribute to bacterial infections in SAM could identify more effective ways of treating malnutrition.