Anti-PD-1 Therapy Alleviates Klebsiella pneumoniae-Induced Liver Abscess by Effectively Activating Kupffer Cells.

Klebsiella pneumoniae-induced liver abscess (KPLA) is the leading cause of pyogenic liver abscess (LA) worldwide. Hepatic Kupffer cells exert protective effects during KPLA progression; thus, elucidating their protective mechanisms and developing novel therapeutic strategies are imperative. A murine KPLA model was established. Hematoxylineosin (HE) staining and tissue bacterial load were analyzed to verify successful K. pneumoniae infection. RT-qPCR, Western blot (WB), and flow cytometry were employed to quantify PD-1 expression in Kupffer cells. PD-1-knockdown Kupffer-cell transfection systems and PD-1-antibody treatment groups were established. Bacterial counts (CFU) and ELISA plus flow cytometry for inflammatory cytokines were used to evaluate the relationship between PD-1 expression and Kupffer-cell bacterial clearance. Finally, the KPLA mouse model was treated with PD-1 antibody to validate the role of PD-1 in LA. In the KPLA mouse model, gross abscess formation was observed, and HE staining revealed disorganized hepatic architecture. PD-1 expression in Kupffer cells was markedly up-regulated, and the proportion of PD-1-positive Kupffer cells increased significantly. In vitro, both PD-1 knockdown and PD-1-antibody treatment enhanced Kupffer-cell bacterial clearance, accompanied by elevated TNF-α, IL-6, and IL-12 levels. In vivo, the PD-1 antibody effectively treated KPLA. KPLA up-regulates PD-1 expression in Kupffer cells, thereby impairing bacterial clearance. Our findings preliminarily indicate that the anti-PD-1 antibody may have application potential in the prevention or early intervention of KPLA.