Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution.

Bacterial quorum-sensing autoinducers are small chemicals released to control microbial community behaviours. N-(3-oxo-dodecanoyl) homoserine lactone, the autoinducer of the Pseudomonas aeruginosa LasI-LasR circuitry, triggers significant cell death in lymphocytes. We found that this molecule is incorporated into the mammalian plasma membrane and induces dissolution of eukaryotic lipid domains.

A phosphatidylinositol 4,5-bisphosphate redistribution-based sensing mechanism initiates a phagocytosis programing.

Phagocytosis is one of the earliest cellular functions, developing approximately 2 billion years ago. Although FcR-based phagocytic signaling is well-studied, how it originated from ancient phagocytosis is unknown. Lipid redistribution upregulates a phagocytic program recapitulating FcR-based phagocytosis with complete dependence on Src family kinases, Syk, and phosphoinositide 3-kinases (PI3K).

A naturally occurring transcript variant of MARCO reveals the SRCR domain is critical for function.

Macrophage receptor with collagenous structure (MARCO) is a class A scavenger receptor (cA-SR) that recognizes and phagocytoses a wide variety of pathogens. Most cA-SRs that contain a C-terminal scavenger receptor cysteine-rich (SRCR) domain use the proximal collagenous domain to bind ligands. In contrast, the role of the SRCR domain of MARCO in phagocytosis, adhesion and pro-inflammatory signaling is less clear.

Activation of NLRP3 inflammasome by crystalline structures via cell surface contact.

Crystalline structures activate the NLRP3 inflammasome, leading to the production of IL-1β, however, the molecular interactions responsible for NLRP3 activation are not fully understood. Cathepsin B release from the ruptured phagolysosome and potassium ion efflux have been suggested to be critical for this activation. Here, we report that Cathepsin B redistribution was not a crucial event in crystal-induced IL-1β production.

MARCO is required for TLR2- and Nod2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx.

Streptococcus pneumoniae is a common human pathogen that accounts for >1 million deaths every year. Colonization of the nasopharynx by S. pneumoniae precedes pulmonary and other invasive diseases and, therefore, is a promising target for intervention.