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Eradication of pathogens from the bloodstream is critical to prevent disseminated infections and sepsis. Kupffer cells in the liver form an intravascular firewall that captures and clears pathogens from the blood. The catching and killing of circulating pathogens by Kupffer cells in vivo are promoted by the gut microbiota. This process is facilitated through commensal-derived D-lactate that reaches the liver via the portal vein.
Administration of purified D-lactate to germ-free mice, or gnotobiotic colonization with D-lactate-producing commensals, restores Kupffer cell-mediated pathogen clearance by the liver firewall.
The integrity of this Kupffer cell-mediated intravascular firewall requires continuous crosstalk with gut commensals. Microbiota depletion with antibiotics leads to a failure of pathogen clearance and results in overwhelming disseminated infection.
NLRP3 Inflammasome is functional in Kupffer cells and Hepatic Stellate Cells (HSC)