Conservation of NLRP3 Inflammasome Pathway in Monotremes and Large-Scale Restructuring of the Caspase-1 Gene Cluster Region in Mammals.

Activation of the NLRP3 inflammasome can be triggered by components of fungi, bacteria and viruses, as well as cellular stress and environmental irritants. The NLRP3 inflammasome has been well characterised in mouse and humans but limited information is available from other mammalian species. To gain a better understanding of the evolution of genes involved in the NLRP3 inflammasome pathway, we examined them in mammalian species representing the three major lineages (eutheria, metatheria and prototheria) and in chicken as an outgroup. Our results show that the inflammasome pathway machinery is generally well conserved in the species examined. We identified four NLRP members in echidna and seven in platypus as well as confirming Nlrp3 is present in marsupials and monotremes. Monotremes feature eleven Dectin family genes that are split across two chromosomes. Only three family members were found in opossum, Tasmanian devil and koala. Of the four Dectin family members known to be involved in the NLRP3 inflammasome pathway only Clec4e (Mincle) was identified in all species examined. Echidna possesses a single copy of Caspase-1 which, alongside previous results reported in the platypus, supports the conclusion that this is the only proinflammatory caspase in the monotremes. Our analysis suggests that Caspase-1 moved to a new chromosomal region in early mammalian evolution. This was followed by expansion of the cluster and accumulation of additional genes. The expansion of key gene families flanking Caspase-1 may have led to an expansion of inflammasome pathways and a more regulated immune system through the CARD genes.