Decoding Host–Pathogen Dynamics in Klebsiella pneumoniae Infections: Mechanisms of Cell Death Regulation and Host-Directed Therapies for Sepsis

Pathogenic microbes utilize virulence strategies to subvert host immune responses, highlighting a continuous race between the pathogen and the host. The emergence of multidrug- resistant and hypervirulent strains of Klebsiella pneumoniae (Kp) poses a critical threat to public health. This critical evaluation identifies key gaps in understanding the interplay between Kp and host innate immunity. This review provides a comprehensive overview of the mechanisms by which Kp triggers various forms of cell death. Dysregulated cell death may exacerbate cytokine release, contributing to the hyperinflammatory response characteristic of sepsis. The rise in antimicrobial resistance (AMR) in Kp necessitates the exploration of alternative therapeutic approaches. This review highlights that immunomodulatory approaches targeting cell death regulators or immune checkpoints may offer host-directed strategies against Kp-induced sepsis. Although novel immunotherapies offer potential to restore immune balance, their clinical applicability remains constrained by limited translational evidence.