The study of pathogenic mechanisms of K.pneumoniae-caused liver abscess in diabetic mice model

• Main Authors: Yi-Chun Lin, 林怡均
• Other Authors: Chuan-Mu Chen
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/01807990096211999777

博士 === 國立中興大學 === 生命科學系所 === 101 === The community-acquired Klebsiella pneumoniae-caused liver abscess (KLA) infection is widespread mainly in the past three decades, especially in Taiwan. The similar prevalence of KLA is also reported in other countries gradually. The infections are predominant tended to occur in diabetic patients. The capsular polysaccharide (CPS) of K. pneumoniae is generally considered to be an important pathogenicity factor. The resulted hypermucoviscosity (HV) is related to the virulent strains of K. pneumoniae, which may circumvent host defenses. However, the emergences of tissue-abscesses-associated HV-negative isolates are noted in clinical infection. To identify the role of mucoviscosity property in the pathogenesis of K. pneumoniae, the diabetic or normal glycemic mice were administered orally or intratracheally with HV-positive or -negative strain. The results exhibited that the HV phenotype was required for the virulence of the clinically isolated HV-positive strain 1112. But the superior ability of the HV-negative stain 1084 over 1112 to cause bacteremia in diabetic mice suggested that the virulence of HV-negative K. pneumoniae may related with other factors, and the host with worsen immune system may play an important role. Although several bacterial characteristics has been contributed with KLA, it is uncertain that the cellular mechanisms relative to the pathogenesis of K. pneumonia infection in the liver. In our KLA mouse model, increased production of interferon-γ (IFN-γ) was significantly evoked by K. pneumoniae infections in the liver. IFN-γ can induce hepatocyte apoptosis or inhibit cell cycle progression, thereby suppressing liver regeneration may act as an essential mediators during liver disease. Next, auto-bioluminescence expressing K. pneumoniae was orally inoculated into diabetic mice and age-match naïve control to study the role of IFN-γ signaling pathway in hepatic response. Moreover, the utilization of in vivo imaging system (IVIS) can real-time detect the bacterial distribution during infection. These results revealed that KLA infection was associated with IFN-γ/signal transducers and activators of transcription (STAT)/IFN regulatory factor-1 (IRF-1) signaling. Inflammatory damage induced in the diabetic mice was enhanced due to massive infiltrates of neutrophils recruited by overproduction of interleukin-1β(IL-1β) and macrophage inflammatory protein-2 (MIP-2), and that was worsened by endoplasmic reticulum stress (ER stress) related liver apoptosis.