Humoral immunity against capsule polysaccharide protects the host from magA+ Klebsiella pneumoniae-induced 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 DeltamagA 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 K1 strains tested but not the DeltamagA and non-K1 strains. Moreover, the anti-CPS MAbs protected mice from magA(+) K. pneumoniae-induced liver abscess formation and lethality. This indicates that the K1 epitope is a promising target for vaccine development, and anti-CPS MAbs has great potential to protect host from K1 strain-induced mortality and morbidity in diabetic and other immunocompromised patients in the future.
Wu
Ming-Fang
MF
Department and Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Yang
Chih-Ya
CY
Lin
Tzu-Lung
TL
Wang
Jin-Town
JT
Yang
Feng-Ling
FL
Wu
Shih-Hsiung
SH
Hu
Bor-Shen
BS
Chou
Teh-Ying
TY
Tsai
Ming-Daw
MD
Lin
Chi-Hung
CH
Hsieh
Shie-Liang
SL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation; D016667:Bacterial Capsules / Q000737:chemistry*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D007710:Klebsiella Infections / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; C501254:MagA protein, Klebsiella pneumoniae; D011135:Polysaccharides, Bacterial; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4