LPS targets host guanylate-binding proteins to the bacterial outer membrane for non-canonical inflammasome activation.

ABSTRACT: Pathogenic and commensal Gram-negative bacteria produce and release outer membrane vesicles (OMVs), which present several surface antigens and play an important role for bacterial pathogenesis. OMVs also modulate the host immune system, which makes them attractive as vaccine candidates. At the cellular level, OMVs are internalized by macrophages and deliver lipopolysaccharide (LPS) into the host cytosol, thus activating the caspase-11 non-canonical inflammasome. Here, we show that OMV-induced inflammasome activation requires TLR4-TRIF signaling, the production of type I interferons, and the action of guanylate-binding proteins (GBPs), both in macrophages and in vivo Mechanistically, we find that isoprenylated GBPs associate with the surface of OMVs or with transfected LPS, indicatin

SUBMITTER: Santos JC 

PROVIDER: S-EPMC5852652 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature