An overview of innate cellular immune responses against hypervirulent Klebsiella pneumoniae: from evasion strategies to liver abscess formation.

Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a redoubtable global pathogen, distinguished from classical K. pneumoniae (cKp) by its ability to cause life-threatening, community-acquired infections in both healthy and immunocompetent individuals. While its pathogenicity is fundamentally anchored in a specialized virulence arsenal - including the K1/K2 capsular serotypes associated with a hypercapsular structure, the hypermucoviscous phenotype, high-affinity siderophores like aerobactin, and mobile genetic elements such as the KpVP plasmid and ICEKp10 - the true hallmark of hvKp is its sophisticated subversion of the innate cellular immune response. This review synthesizes current evidence on the mechanistic interactions between hvKp and host immune effectors, detailing a cell-by-cell evasion strategy. We highlight how hvKp manipulates neutrophils through the induction of immunosuppressive PD-L1+/Siglec-H+ subpopulations and the strategic delay of apoptosis. Furthermore, we discuss the hijacking of macrophage metabolism, specifically iron and lipid pathways, in addition to inducing dysfunctional M(Kp) macrophage polarization and the formation of the Klebsiella-containing vacuole, which facilitates intracellular survival and replication. Rather than acting as isolated events, we analyze how these cell-specific evasion strategies serve as the foundational chronological checkpoints of pathogenesis. Integrating these mechanisms, we establish an interconnected narrative that culminates in a comprehensive, time-dependent model of pyogenic liver abscess formation, mapping the step-wise progression from portal translocation to host pyroptosis and microabscess consolidation. Finally, we propose that targeting these specific host-pathogen interfaces offers a promising frontier for host-directed therapies.