臺大醫院-內科部;臺大醫學院-微生物學科暨研究所;Hua, Kuo-FengKuo-FengHuaYang, Feng-LingFeng-LingYangChiu, Hsiao-WenHsiao-WenChiuChou, Ju-ChingJu-ChingChouDong, Wei-ChihWei-ChihDongLin, Chien-NanChien-NanLinLin, Chai-YiChai-YiLinJIN-TOWN WANGLi, Lan-HuiLan-HuiLiChiu, Huan-WenHuan-WenChiuChiu, Yi-ChichYi-ChichChiuWu, Shih-HsiungShih-HsiungWuMcCormick, B. A.B. A.McCormick2017-02-152018-07-112017-02-152018-07-112015http://ntur.lib.ntu.edu.tw//handle/246246/270683Klebsiella pneumoniae (strain 43816, K2 serotype) induces interleukin-1 beta (IL-1 beta) secretion, but neither the bacterial factor triggering the activation of these inflammasome-dependent responses nor whether they are mediated by NLRP3 or NLRC4 is known. In this study, we identified a capsular polysaccharide (K1-CPS) in K. pneumoniae (NTUH-K2044, K1 serotype), isolated from a primary pyogenic liver abscess (PLA K. pneumoniae), as the Klebsiella factor that induces IL-1 beta secretion in an NLRP3-, ASC-, and caspase-1-dependent manner in macrophages. K1-CPS induced NLRP3 inflammasome activation through reactive oxygen species (ROS) generation, mitogen-activated protein kinase phosphorylation, and NF-kappa B activation. Inhibition of both the mitochondrial membrane permeability transition and mitochondrial ROS generation inhibited K1-CPS-mediated NLRP3 inflammasome activation. Furthermore, IL-1 beta secretion in macrophages infected with PLA K. pneumoniae was shown to depend on NLRP3 but also on NLRC4 and TLR4. In macrophages infected with a K1-CPS deficiency mutant, an lipopolysaccharide (LPS) deficiency mutant, or K1-CPS and LPS double mutants, IL-1 beta secretion levels were lower than those in cells infected with wild-type PLA K. pneumoniae. Our findings indicate that K1-CPS is one of the Klebsiella factors of PLA K. pneumoniae that induce IL-1 beta secretion through the NLRP3 inflammasome.[SDGs]SDG3[SDGs]SDG1510.1128/IAI.00125-15