Nucleotide-binding Leucine-rich Receptor Research Articles

The origin and evolution of a plant resistosome.

The nucleotide-binding, leucine-rich receptor (NLR) protein HOPZ-ACTIVATED RESISTANCE 1 (ZAR1), an immune receptor, interacts with HOPZ-ETI-DEFICIENT 1 (ZED1)-related kinases (ZRKs) and AVRPPHB SUSCEPTIBLE 1-like proteins to form a pentameric resistosome, triggering immune responses. Here, we show that ZAR1 emerged through gene duplication and that ZRKs were derived from the cell surface immune receptors wall-associated protein kinases (WAKs) through the loss of the extracellular domain before the split of eudicots and monocots during the Jurassic period. Many angiosperm ZAR1 orthologs, but not ZAR1 paralogs, are capable of oligomerization in the presence of AtZRKs and triggering cell death, suggesting that the functional ZAR1 resistosome might have originated during the early evolution of angiosperms. Surprisingly, inter-specific pairing of ZAR1 and AtZRKs sometimes results in the formation of a resistosome in the absence of pathogen stimulation, suggesting within-species compatibility between ZAR1 and ZRKs as a result of co-evolution. Numerous concerted losses of ZAR1 and ZRKs occurred in angiosperms, further supporting the ancient co-evolution between ZAR1 and ZRKs. Our findings provide insights into the origin of new plant immune surveillance networks.

NLRP3 directs inflammasome activation in response to live F. tularensis infection (42.20)

Abstract Detection of intracellular pathogens is facilitated by members of the nucleotide binding-leucine rich receptor (NLR) family. The role of ASC/Caspase-1 axis for protective innate immunity against Francisella infection is well established, however the NLR(s) involved in initiation of innate immune responses during Francisella infection are yet unknown. Here we demonstrate that human NLRP3 mediates inflammasome dependent IL-1β production following Francisella infection. Notably, both human NLRP3 and mouse Nlrp3 are sufficient to assemble functional inflammasomes in HEK293T cells infected with Francisella. Furthermore, our results also support the existence of more than one Francisella-responsive cytoplasmic inflammasome complex and suggest that intrinsic differences in bacterial strains as well as monocyte-macrophage differentiation status influence inflammasome-dependent innate immune responses to Francisella.