Humoral immunity against capsule polysaccharide protects the host from magA⁺ Klebsiella pneumoniae-lnduced lethal disease by evading toll-like receptor 4 signaling

Klebsiella pneumoniae magA (for mucoviscosity-associated gene A) is linked to the pathogenesis of primary pyogenic liver abscess, but the underlying mechanism by which magA increases pathogenicity is not well elucidated. In this study, we investigated the role of the capsular polysaccharides (CPS) in the pathogenesis of magA⁺ K. pneumoniae by comparing host immunity to magA⁺ K. pneumoniae and a ΔmagA mutant. We found that Toll-like receptor 4 recognition by magA⁺ K pneumoniae was hampered by the mucoviscosity of the magA ⁺ K. pneumoniae CPS. Interestingly, monoclonal antibodies (MAbs) against magA⁺ K pneumoniae CPS recognized all of the Kl strains tested but not the ΔmagA and non-Kl strains. Moreover, the anti-CPS MAbs protected mice from magA⁺ K. pneumoniae-induced liver abscess formation and lethality. This indicates that the Kl epitope is a promising target for vaccine development, and anti-CPS MAbs has great potential to protect host from Kl strain-induced mortality and morbidity in diabetic and other immunocompromised patients in the future.