INFLUENCE OF METABOLIC PROFILE, NUTRIENT SENSING AND EXOGENOUS FACTORS ON IMMUNE RESPONSES TO XENOBIOTICS AND EXOGENOUS MATERIALS

Activation of immune cells, results in alteration of energy and nutrient requirements in order to provide sufficient energy resource for the cells and biomass for replication and protein synthesis. Upon activation, immune cells increase their uptake of glucose in order to power cellular processes by glycolysis. Glucose uptake is, primarily, accomplished by the glucose uptake transporters GLUT1 and GLUT4. Recent work, from the group, has shown that the antiretroviral drugs Efavirenz and Lopinavir can inhibit the activation of primary immune cells. Additionally, nanoformulations of these drugs appear to mitigate some of these processes. We are determining the activity of metabolite transporters in the metabolic responses to immunological challenges and assessing the long-term implications of exposure to xenobiotics on metabolic profiles.

Additionally, other factors within the local environment may influecne immune cell behaviour. Exosomes are nano-sized, extracellular vesicles that are involved in intercellular communication and are generally thought to be involved in immune homeostasis. Their presence in, multiple, biological fluids suggests their importance in controlling the immune response. We have shown that the presence of so-called “tolerosomes” in the plasma may dampen the immunological response of human immune cells to pro-inflammatory stimuli. The aim of this work is to ascertain further the impact of tolerosomes on immunological responses to stimuli, as well as engineered nanobiomaterials, to further our understanding of interindividual responses to treatments.