Inflammasomes in Myeloid Cells: Warriors Within

Abstract

The inflammasome is a large multimeric protein complex comprised of an effector protein that demonstrates a specificity for a variety of activators or ligands, an adaptor molecule and pro-caspase-1 which is converted to caspase-1 upon inflammasome activation. Inflammasomes are expressed primarily by myeloid cells and are located within the cell. The macromolecular inflammasome structure can be visualized by cryo-electron microscopy. This complex has been found to play a role in a variety of disease models in mice and several have been genetically linked to human diseases. In most cases, the effector protein is a member of the NLR (nucleotide-binding domain leucine rich repeat containing), or NOD (nucleotide oligomerization domain)-like receptor protein family. However, other effectors have also been described, with the most notable being AIM2 (absence in melanoma 2), which recognizes DNA to elicit inflammasome function. This chapter will focus on the role of the inflammasome in myeloid cells and its role in health and disease.

Caspase-1 from Human Myeloid-Derived Suppressor Cells Can Promote T Cell–Independent Tumor Proliferation

“…In other models, however, NLRP3 null mice had reduced lung metastasis with B16-F10 tumor cells (46). These examples highlight the complex association between the inflammasome complex and cancer, which were have been reviewed in detail (47)(48)(49).…”

Bidirectional Role of NLRP3 During Acute and Chronic Cholestatic Liver Injury

“…By performing F4/80 and IL-1β co-staining experiments we found that IL-1β expression is especially found in macrophages (Supplemental Figure 1a). 23,24 Increased liver injury after acute BDL in Nlrp3-deficient mice.…”

Frontline Science: Staphylococcus aureus promotes receptor-interacting protein kinase 3- and protease-dependent production of IL-1β in human neutrophils

“…In contrast to PMN responses to nigericin, PMN‐SA secretion of IL‐1β occurred without concomitant IL‐18 release, an unexpected observation. Once assembled and activated, NLRP3, the most extensively studied inflammasome in myeloid cells, processes procaspase‐1 to active caspase‐1, the enzymatically active form that in turn cleaves both pro‐IL‐1β and pro‐IL‐18 to yield the mature species secreted extracellularly . Given that prior work by Bakele et al .…”

“…In general, the proteolytic maturation of pro‐IL‐1β and pro‐IL‐18 and secretion of the mature cytokines depend on active caspase‐1 and an inflammasome, a multicomponent protein complex that cleaves procaspase‐1 . Staphylococcus aureus (SA) stimulates IL‐1β secretion from macrophages by activation of caspase‐1 and the NLRP3 inflammasome, the most extensively studied inflammasome in myeloid cells . In contrast to the extensive studies of macrophage responses, the presence and importance of NLRP3 and IL‐1β production by human PMN have infrequently been examined.…”

“…9 Staphylococcus aureus (SA) stimulates IL-1 secretion from macrophages by activation of caspase-1 and the NLRP3 inflammasome, the most extensively studied inflammasome in myeloid cells. 10,11 In contrast to the extensive studies of macrophage responses, the presence and importance of NLRP3 and IL-1 production by human PMN have infrequently been examined.…”