Macrophages, rather than DCs, are responsible for inflammasome activity in the GM-CSF BMDC model

Inflammasomes are one of the most important mechanisms for innate immune defense against microbial infection but are also known to drive various inflammatory disorders via processing and release of the cytokine IL-1β. As research into the regulation and effects of inflammasomes in disease has rapidly expanded, a variety of cell types, including dendritic cells (DCs), have been suggested to be inflammasome competent. Here we describe a major fault in the widely used DC–inflammasome model of bone marrow–derived dendritic cells (BMDCs) generated with the cytokine granulocyte–macrophage colony-stimulating factor (GM-CSF). We found that among GM-CSF bone marrow–derived cell populations, monocyte-derived macrophages, rather than BMDCs, were responsible for inflammasome activation and IL-1β secretion. Therefore, GM-CSF bone marrow–derived cells should not be used to draw conclusions about DC-dependent inflammasome biology, although they remain a useful tool for analysis of inflammasome responses in monocytes–macrophages. Dendritic cells (DCs) have been suggested to express a functional NLRP3 inflammasome. Gerlic and colleagues demonstrate, however, that bone marrow–derived DCs completely lack NLRP3 inflammasome activity and that the bulk of splenic DCs lack or have only minimal activity.