A spike in inflammation

The innate immune system is the first line of defence against invading microorganisms. Specialized immune cells, primarily myeloid cells, sense conserved pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) to coordinate an immune response. One important class of PRRs is the nucleotide-binding domain and leucine-rich-repeat (NLR) proteins. In the presence of pathogens, NLR proteins trigger the formation of the inflammasome. This large macromolecular complex has caspase-1 activity, which stimulates production of the inflammatory cytokines interleukin (IL)-1β and IL-18, leading to inflammation and inflammatory cell death (pyroptosis). Extensive work has characterized the biochemical cues that activate immunity through PRRs such as NLRs. However, in addition to conserved molecular patterns, pathogens also adopt conserved shapes and surface structures. For example, some bacteria have complex surface topographies created through nanofeatures such as flagella, pili and fimbriae. It has long been hypothesized that these physical cues are also sensed by the immune system through PRRs, but definitive experimental proof has remained elusive, partly because of the difficulties in separating the physical and biochemical immunological inputs produced by these natural structures