Increased pneumonia-associated pulmonary barrier dysfunction in type 2 diabetes

Individuals with obesity-related type 2 diabetes (T2D) are significantly more susceptible to pneumonia-associated mortality and morbidity than healthy subjects, but the reasons for this remain unknown. Complications in T2D patients with pneumonia involve the accumulation of liquid (edema) in the lung sacs, caused by an increased leak of the tiny blood vessels (capillaries) in the lungs, the latter of which are responsible for the uptake of oxygen.This application wants to unravel the underlying mechanism involved in the increased susceptibility of T2D patients to pneumonia-associated lung edema formation. In preliminary data, it was observed that T2D mice are significantly more susceptible to leak of the lung capillaries caused by a bacterial toxin that is released during antibiotic treatment of pneumonia patients. We will compare edema formation between transgenic mice with T2D and control mice, treated with the pneumococcal toxin pneumolysin and we will investigate our hypothesis that increased sensitivity in T2D animals is caused by increased generation of toxic reactive oxygen radicals in their lung capillaries. As such, this application can identify new therapeutic targets to reduce complications of pneumonia in patients with T2D.