Lung MDSC-derived IL-10 in resolution of inflammation during bacterial pneumonia (INM2P.420)

Bacterial pneumonia remains a significant burden worldwide. Although an inflammatory response in the lung is required to fight against pathogenic microorganisms, persistent inflammation leads to collateral tissue damage and precipitates acute lung injury. Recently we have shown that interleukin (IL)-10 is essential for resolution of lung inflammation with Klebsiella pneumoniae, a bacterium commonly associated with hospital-acquired pneumonia. Although IL-10-/- mice cleared bacteria, they displayed increased morbidity with progressive weight loss and persistent lung inflammation in the later phase after infection. A source of tissue IL-10 was found to be resident CD11b+Gr1(Ly6G)intF4/80+ cells resembling myeloid-derived suppressor cells (MDSCs). These cells efficiently efferocytosed apoptotic neutrophils, which was aided by IL-10. However, our ongoing studies show that IL-10 production from lung MDSCs can be negatively regulated during pneumonia. Previous studies have documented increased levels of the lipid cardiolipin, which is generated from the mitochondria of dead cells, in the lungs of patients with severe pneumonia. We have observed that cardiolipin blunts pulmonary IL-10 production thereby compromising the efficiency of the MDSC-IL-10 system to dampen inflammation. Considering the important role of IL-10 in limiting inflammation and tissue damage, our study identifies new targets for maintaining IL-10 expression during resolution of inflammation in pneumonia.