| Summary: | 碩士 === 中山醫學大學 === 免疫學研究所 === 95 === Klebsiella pneumoniae, an important pathogen belonging to Gram-negative Enterobacteriaceae, usually causes community- and hospital-acquired infections. In Taiwan, diabetic patients have an increased susceptibility to K. pneumoniae infections combined with several clinical syndromes, including primary pneumonia, pyogenic liver abscess, meningitis and metastatic endophthalmitis, and their high mortalities, K. pneumoniae-induced liver abscess in diabetic patients become an important infectious disease in Taiwan. The virulence factors of K. pneumoniae identified include capsule, lipopolysaccharide (LPS) et al., however, the dominant pathogenic factor(s) was (were) still unclear. On the other hand, the host factors involved in pathogenesis of K. pneumoniae-induced liver abscess associated with diabetes mellitus also remain to be clarified. For studying the host effect(s) of diabetes on K. pneumoniae-induced liver abscess, we evaluated the innate immune activities of diabetes mellitus patients or diabetic mice and evaluated the responses of liver tissue to K. pneumoniae infection. Our results indicated the abilities of phagocytosis of neutrophils and macrophages from diabetic patients decreased. The migration capabilities and survival rates of both immune cells from diabetic mice were also less than those obtained from non-diabetic mice. Comparing the survival rates, K. pneumoniae-infected diabetic mice had a higher fatality rate with K. pneumoniae-infection than control non-diabetic mice. After infected with K. pneumoniae with viscoid capsule, the interspace between the hepatocytes of diabetic mice were formed as cleft, however, hyper-mucoid K. pneumoniae caused lots of vacuoles within hepatic tissues in diabetic mice but not non-diabetic groups. Furthermore, we evaluated the activities of intracellular signal pathways in hepatic tissues. After oral administration with K. pneumoniae, caspase 3 activity was detected in liver samples from K. pneumoniae-infected diabetic mice but not other groups. Interestingly, activities of Erk and p38 were more higher in hepatic tissues from diabetic mice than those samples from non-diabetic mice. Whether mice were K. pneumoniae-infected, unfolded protein responses (UPR) in liver samples of non-diabetic mice were more active than in diabetic mouse livers, and the autophagy were also be deteted in diabetic mouse liver tissues. To evaluate the direct cytopathic effects of K. pneumoniae in vitro, HepG2 or BNL cells were cocultured with K. pneumoniae and the apoptosis of these cells were the determined. Our results indicated that the DNA framgmentation increased in a dose dependent manner by live but not dead microorganisms. We proposed that capsule maybe play a role in hepatic cytopathy. Taken together, except specific virulent factors of K. pneumoniae, the immunocompromise and low stress-defenses in diabetes mellitus may also result in K. pneumoniae-induced liver abscess.
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