Vascular traffic control of neutrophil recruitment to the liver by microbiota-endothelium crosstalk

Vascular traffic control of neutrophil recruitment to the liver by microbiota-endothelium crosstalk

Blog Article

Right Handlebar Summary: During bloodstream infections, neutrophils home to the liver as part of an intravascular immune response to eradicate blood-borne pathogens, but the mechanisms regulating this crucial response are unknown.Using in vivo imaging of neutrophil trafficking in germ-free and gnotobiotic mice, we demonstrate that the intestinal microbiota guides neutrophil homing to the liver in response to infection mediated by the microbial metabolite D-lactate.Commensal-derived D-lactate augments neutrophil adhesion in the liver independent of granulopoiesis in bone marrow or neutrophil maturation and activation in blood.Instead, gut-to-liver D-lactate signaling primes liver endothelial cells to upregulate adhesion molecule expression in response to infection and promote neutrophil adherence.Targeted correction of microbiota D-lactate production in a model of antibiotic-induced dysbiosis restores ORG RAW HAZELNUTS neutrophil homing to the liver and reduces bacteremia in a model of Staphylococcus aureus infection.

These findings reveal long-distance traffic control of neutrophil recruitment to the liver by microbiota-endothelium crosstalk.