Insights into assembly of the macromolecular inflammasome complex

Dramatic advances in our understanding of the ultrastructure of the inflammasome and the molecular interactions involved in its assembly have recently been made. The adaptor protein ASC has been proposed to display prion-like activity that results in the formation of filamentous structures in the cell. These filamentouos structures can subsequently become inflammatory themselves if released into the extracellular space and then phagocytosed. Various groups have now utilised a variety of microscopy and structural approaches in order to visualise components of, and indeed the entire, inflammasome in both endogenous and overexpression systems. In this brief review we draw upon these new pieces of work to describe how our understanding of the global structure of the inflammasome has progressed in light of these new observations. In particular we begin by providing an initial perspective on the possible formation of small circular, wheel-like, oligomers resembling apoptosomes. We then address the current view that inflammasomes result from the formation of a much larger complex which may involve polymeric filaments. We discuss how these developments fit with recent theories of inflammatory signalling, what questions these advances raise, and propose key areas for further investigation.