Orchestration of human macrophage NLRP3 inflammasome activation by Staphylococcus aureus extracellular vesicles.

ABSTRACT: Release of extracellular vesicles (EVs) is a common feature among eukaryotes, archaea, and bacteria. However, the biogenesis and downstream biological effects of EVs released from gram-positive bacteria remain poorly characterized. Here, we report that EVs purified from a community-associated methicillin-resistant Staphylococcus aureus strain were internalized into human macrophages in vitro and that this process was blocked by inhibition of the dynamin-dependent endocytic pathway. Human macrophages responded to S. aureus EVs by TLR2 signaling and activation of NLRP3 inflammasomes through K⁺ efflux, leading to the recruitment of ASC and activation of caspase-1. Cleavage of pro-interleukin (IL)-1β, pro-IL-18, and gasdermin-D by activated caspase-1 resulted in the ce

SUBMITTER: Wang X 

PROVIDER: S-EPMC7022218 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature