Microvesicular caspase-1 mediates lymphocyte apoptosis in sepsis.

Objective: Immune dysregulation during sepsis is poorly understood, however, lymphocyte apoptosis has been shown to correlate with poor outcomes in septic patients. The inflammasome, a molecular complex which includes caspase-1, is essential to the innate immune response to infection and also important in sepsis induced apoptosis. Our group has recently demonstrated that endotoxin-stimulated monocytes release microvesicles (MVs) containing caspase-1 that are capable of inducing apoptosis.

Pyrin critical to macrophage IL-1beta response to Francisella challenge.

Relative to monocytes, human macrophages are deficient in their ability to process and release IL-1beta. In an effort to explain this difference, we used a model of IL-1beta processing and release that is dependent upon bacterial escape into the cytosol. Fresh human blood monocytes were compared with monocyte-derived macrophages (MDM) for their IL-1beta release in response to challenge with Francisella novicida.