Humoral Immunity against Capsule Polysaccharide Protects the Host from magA+ Klebsiella pneumoniae-Induced Lethal Disease by Evading Toll-Like Receptor 4 Signaling

被引:34
作者
Wu, Ming-Fang [1 ,10 ]
Yang, Chih-Ya [1 ,10 ]
Lin, Tzu-Lung [2 ]
Wang, Jin-Town [2 ,3 ]
Yang, Feng-Ling [4 ]
Wu, Shih-Hsiung [4 ]
Hu, Bor-Shen [5 ]
Chou, Teh-Ying [6 ,7 ]
Tsai, Ming-Daw [4 ,8 ]
Lin, Chi-Hung [1 ,10 ]
Hsieh, Shie-Liang [1 ,8 ,9 ,10 ]
机构
[1] Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 11221, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Microbiol, Taipei, Taiwan
[3] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan
[4] Acad Sinica, Inst Biol Chem, Taipei, Taiwan
[5] Taipei City Hosp, Heping Branch, Dept Internal Med, Infect Dis Sect, Taipei, Taiwan
[6] Taipei Vet Gen Hosp, Dept Pathol, Surg Pathol Sect, Taipei, Taiwan
[7] Taipei Vet Gen Hosp, Lab Med, Taipei, Taiwan
[8] Acad Sinica, Genom Res Ctr, Taipei, Taiwan
[9] Natl Yang Ming Univ, Immunol Res Ctr, Taipei 11221, Taiwan
[10] Natl Yang Ming Univ, Dept Microbiol & Immunol, Taipei 11221, Taiwan
关键词
PYOGENIC LIVER-ABSCESS; SEPTIC ENDOPHTHALMITIS; EMERGING DISEASE; MENINGITIS; BACTEREMIA; VIRULENCE; RECOGNITION; SALMONELLA; ACTIVATION; EXPRESSION;
D O I
10.1128/IAI.00931-08
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 Delta magA 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 Delta magA 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.
引用
收藏
页码:615 / 621
页数:7
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