The identification of cytokine-activating ‘inflammasomes’ has revolutionised our understanding of molecular circuits linking pathogen/danger sensing, cytokine production and immune system activation in host defence, and dysregulation of these processes in human heritable and acquired disease. While the last decade has witnessed great advances in our understanding of the molecular pathways triggering caspase-1 activation and cytokine maturation by inflammasomes during infection, the cellular drivers of these pathways that are fundamental to in vivo host defence are still unclear. In this study, we systematically profiled the suite of inflammasomes expressed in human and mouse cells of the innate and adaptive immune system, and studied the contribution of individual cell types to inflammasome-mediated host defence in vitro and in vivo. Our data reveal surprising cell type specificity to the pathways engaged by inflammasomes upon infection, and suggest an elegant interplay between innate immune cells for co-ordinating inflammasome-dependent immune defence in vivo.