GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE312nnn/GSE312076/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312076GEOGSEfalseZone-specific hepatocytes orchestrate the early onset of host defence mechanisms during Staphylococcus aureus bloodstream infectionBloodstream infections (BSI) cause substantial morbidity and mortality, with Staphylococcus aureus among the most lethal pathogens. 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. These findings demonstrate that hepatocyte zonation orchestrates early hepatic immune responses during S. aureus BSI.2026/04/07GSE312076GSM9337359GSM9337358GSM933735734328312076Mus musculus