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

Year: 2026
Type: article
Abstract: 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 upregulated, 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.
Language: English
Field: Medicine
Open Access status: bronze
OpenAlex ID: W7222936044
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Cites: 26
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Related to: 10