Supporting dataset for "The T6SS Effector Hcp of Hypervirulent Klebsiella pneumoniae Exacerbates Liver Abscess by Inducing Macrophage-HMGB1/RAGE-Dependent Endothelial Pyroptosis": original Western blot images, cytokine ELISA data, mouse survival analysis, and raw numerical data

Hypervirulent <i>Klebsiella pneumoniae (hvKP)</i> causes pyogenic liver abscess and fulminant sepsis via vascular endothelial dysfunction and injury. This study aimed to elucidate how its type VI secretion system (T6SS) effector hemolysin-coregulated protein (Hcp) compromises vascular dysfunction by inducing endothelial pyroptosis. We stimulated macrophages with Hcp or <i>hvKP </i>strains (wild-type/hcp-knockout/ complemented), then applied supernatants to human umbilical vein endothelial cells (HUVECs) to evaluate pyroptosis, cytokine release, and endothelial activation. Mechanistic validation studies employed high-mobility group box 1 (HMGB1)⁻/⁻ macrophages, caspase-1⁻/⁻ HUVECs, and pharmacological inhibitors, including a receptor for advanced glycation end products (RAGE) inhibitor (FPS-ZM1) and an HMGB1-neutralizing antibody. A murine hvKP liver abscess model assessed survival, HMGB1 dynamics, and vascular pathology. Hcp post-translationally stimulated macrophage HMGB1 secretion. The resulting Hcp–HMGB1 complexes were internalized by HUVECs via RAGE, thereby inducing pyroptosis and the release of interleukin (IL)-1β and IL-18 through the canonical pyroptotic pathway. These effects were abolished by HMGB1 knockout, caspase-1 deficiency, or RAGE inhibition. Additionally, Hcp upregulated endothelial activation markers in an HMGB1-dependent manner. Mice infected with hcp-knockout hvKP showed improved survival rates, lower serum HMGB1 levels, and reduced endothelial injury. Thus, the T6SS effector Hcp drives endothelial pyroptosis through macrophage-derived HMGB1- and RAGE-mediated signaling, establishing the Hcp–HMGB1–RAGE–caspase-1 axis as a promising therapeutic target for hvKP-associated vascular injury.