Zone-specific hepatocytes orchestrate the early onset of host immune defenses during
Staphylococcus aureus
bloodstream infection
Obageli V. Nwofor, Alexander Leipold, Qian Chen, Robert Geffers, Antoine-Emmanuel Saliba, Oliver Goldmann, Eva Medina
Publication in
Frontiers in Immunology
Background
Bloodstream infections (BSI) are life-threatening conditions initiated by pathogens entering the circulation, with
Staphylococcus aureus
among the most lethal causative agents. The liver is the primary site for the initial detection and clearance of blood-borne pathogens. Emerging evidence indicates that the hepatic immune response to pathological insults is influenced by liver zonation, exhibiting both spatial and cellular specialization. Because direct experimental evidence linking liver zonation to the immune response to BSI is currently lacking, this study aimed to characterize the compartmentalization of the early immune response in the liver to blood-borne
S. aureus.
Key Biological Findings
-
The liver rapidly sequesterd ~90% of circulating
S. aureus
within 4 hours, and markedly reduced bacterial loads by 24 hours of infection.
-
Periportal and midzonal hepatocytes
displayed the strongest transcriptional activation.
-
Pericentral hepatocytes
exhibited delayed and weaker responses.
- Hepatocytes emerged as central orchestrators of the acute-phase response.
-
Chemokine production was compartmentalized across hepatocytes, Kupffer cells,
and liver sinusoidal endothelial cells.
-
Bmper
was identified as a strongly induced zonated response gene during infection in hepatocytes.
Interactive Exploration
- The first plot allows to explore the Cell Atlas split by condition (Ctrl, 4h infection, 24h infection).
- Expression of genes can be explored on the UMAP across conditions.
- Differential expression analysis results can be explored in form of tables. The nomenclature of tables follows following rule: Celltype_Condition1_Condition2
- A BubblePlot allows comprehensive exploration of expression of selected genes across celltypes & conditions.