Diabetics have a higher risk of various infectious diseases including pneumonia.1-3 Current estimates suggest that 450 million people worldwide have diabetes, and this number will increase to approximately 700 million by 2045.4 The increase in diabetes prevalence is thus likely to cause an increase in pneumonia-related morbidity and mortality. A better understanding of the mechanisms underlying diabetes-related dysregulation of the antibacterial immune response may allow to develop more targeted prophylactic strategies to prevent pneumonia in diabetic individuals.
Lower respiratory tract infections represent the fifth leading cause of death worldwide. In the coming years, pneumonia-associated morbidity and mortality may continue to rise as the number of individuals with risk factors for pneumonia, such as diabetes mellitus (among others) growths in many parts of the world.4 However, the mechanism underlying the enhanced susceptibility of diabetic patients to pneumonia is incompletely understood. Preliminary results indicate that diabetic animals exhibit decreased IFNg production and influx of monocyte-derived macrophages into the lung and are higher susceptibility to Legionella pneumophila infection. Moreover, IFNs are crucial for innate defense against L. pneumophila infection.5,6 The aim of the proposed project is to further characterize the impact of diabetes on early IFN-dependent antibacterial immune defense. A better understanding of these mechanisms has the potential to enable more targeted prophylactic strategies to prevent pneumonia in individuals with diabetes mellitus.
Aim 1: To characterize the effect of diabetes mellitus on susceptibility towards L. pneumophila:
Aim 2: To characterize the effect of diabetes mellitus on IFN-dependent defense:
Aim 3: To explore prophylactic intervention strategies to rescue impaired antibacterial immunity in diabetic animals – treatment with e.g. rIFNg, rIL-12 or rIL-18 in diabetic animals and controls to rescue antibacterial defense