Perspectives on the immune response during pneumonia

Pneumonia – an infection of the lung – is a disease that despite great progress in medical research causes many people to become ill. In fact, pneumonia is the leading infectious cause of death worldwide. Despite treatment with antibiotics and supportive care, each year up to 2.5 million people do not survive the consequences of lung infection. Therefore, novel strategies to better recognise and treat severe illness in pneumonia are needed. This thesis worked with different approaches to research the host response during pneumonia as a potential diagnostic and therapeutic target. First, a large cohort of patients admitted to the intensive care unit with severe pneumonia was studied, in which the systemic host response was investigated by measuring a set of biomarkers – indicative of innate immune responses – in blood plasma, and by analysing gene expression profiles in blood leukocytes. Second, cell metabolism mediators involved in the host response during pneumonia were explored, with a special focus on glucose metabolism. By generating conditional knockout mice – mice that lack a particular protein in one cell type, the role of GLUT1, HIF1α and LKB1 during the immunological response was studied. The results of this thesis present new perspectives on the immune response during pneumonia, to provide a better understanding of the pathogenesis of this disease and to explore clues for potential diagnostic and therapeutic targets.