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. Here, we show that the catching and killing of circulating pathogens by Kupffer cells in vivo are promoted by the gut microbiota through commensal-derived D-lactate that reaches the liver via the portal vein. The integrity of this Kupffer cell-mediated intravascular firewall requires continuous crosstalk with gut commensals, as microbiota depletion with antibiotics leads to a failure of pathogen clearance and overwhelming disseminated infection. Furthermore, 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. Thus, the gut microbiota programs an intravascular immune firewall that protects against the spread of bacterial infections via the bloodstream.

从血液中清除病原体对于防止传播性感染和败血症至关重要。肝脏中的枯否细胞形成血管内防火墙，从血液中捕获和清除病原体。在这里，我们显示了库普弗细胞在体内捕获和杀死循环病原体由肠道微生物通过经门静脉到达肝脏的经共生的D-乳酸促进。这种枯否细胞介导的血管内防火墙的完整性需要与肠道保持连续的串扰，因为抗生素对微生物群的耗竭会导致病原体清除失败和压倒性的传播感染。此外，向无菌小鼠施用纯化的D-乳酸盐，或用产生D-乳酸盐的配方进行生菌定植，可恢复肝防火墙对Kupffer细胞介导的病原体的清除作用。因此，肠道菌群可对血管内免疫防火墙编程，以防止细菌感染通过血流传播。