The neutrophil inflammasome

Abstract Since inflammasomes were discovered in the early 21st century, knowledge about their biology has multiplied exponentially. These cytosolic multiprotein complexes alert the immune system about the presence of infection or tissue damage, and regulate the subsequent inflammatory responses. As inflammasome dysregulation is increasingly associated with numerous autoinflammatory disorders, there is an urgent need for further research into the inflammasome’s involvement in the pathogenesis of such diseases in order to identify novel therapeutic targets and treatments. The zebrafish has become a widely used animal model to study human diseases in recent years, and has already provided relevant findings in the field of inflammasome biology including the identification of new components and pathways. We provide a detailed analysis of current knowledge on neutrophil inflammasome biology and compare its features with those of the better known macrophage inflammasome, focusing on its contribution to innate immunity and its relevance for human health. Importantly, a large body of evidence points to a link between neutrophil inflammasome dysfunction and many neutrophil-mediated human diseases, but the real contribution of the neutrophil inflammasome to the pathogenesis of these disorders is largely unknown. Although neutrophils have remained in the shadow of macrophages and monocytes in the field of inflammasome research since the discovery of these multiprotein platforms, recent studies strongly suggest that the importance of the neutrophil inflammasome has been underestimated.