Zone-specific hepatocytes orchestrate the early onset of host defence mechanisms during Staphylococcus aureus bloodstream infection

The liver plays a central role in host defence against blood-borne microbes, yet how its zonal organization shapes this response remains unclear. In a murine model of S. aureus bacteraemia, the liver sequestered ~90% of bacteria within 4 h and markedly reduced bacterial loads by 24 h, indicating rapid activation of local immune defences.

Single-cell RNA sequencing identified periportal and midzonal hepatocytes, and to a lesser extent pericentral hepatocytes, as the principal responders. Besides acute-phase proteins, periportal and midzonal hepatocytes strongly upregulated Bmper, a regulator of bone morphogenetic protein signalling and a likely new mediator of the hepatic acute-phase response. Expansion of Kupffer cells, essential for bacterial clearance, was also observed and was primarily driven by local proliferation.