Abstract：
: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.
journal_name
Cell Host Microbejournal_title
Cell host & microbeauthors
McDonald B,Zucoloto AZ,Yu IL,Burkhard R,Brown K,Geuking MB,McCoy KDdoi
10.1016/j.chom.2020.07.014subject
Has Abstractpub_date
2020-11-11 00:00:00pages
660-668.e4issue
5eissn
1931-3128issn
1934-6069pii
S1931-3128(20)30410-8journal_volume
28pub_type
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