Anserine restores antibacterial immunity in cirrhosis via protective CCL5-mediated hepatocyte-CD44(+) pDC crosstalk.

Anserine supplementation restores antibacterial immunity in cirrhotic mice by upregulating hepatocyte CCL5, replenishing CD44+ plasmacytoid dendritic cells, and reducing bacterial burden and mortality.

• Why it matters: Cirrhosis is linked to increased bacterial infection susceptibility, but the dysregulated liver cell crosstalk and metabolic-immune mechanisms driving impaired antibacterial defense remain unclear.
• What they did: The study used scRNA-seq in control and cirrhotic mice with or without bacterial infection, then validated inferred interactions with flow cytometry, targeted metabolomics, and functional assays including ex vivo co-culture, adoptive transfer, antibody blockade, and transgenic models.
• The result: CD44+ pDCs sensed pathogens via TLR7/9 to secrete type I IFN-α, promoting macrophage chemotaxis, ROS production, and phagocytosis through the CCL5-CCR5 axis; human multi-omics and the CATCH-LIFE cohort showed CCL5, anserine, and CD44+ pDC levels correlated with infection incidence and clinical outcomes.

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