Capsular Polysaccharide Is Involved in NLRP3 Inflammasome Activation by Klebsiella pneumoniae Serotype K1
Resource
Infect. Immun., 83(9), 3396-3409
Journal
Infection and Immunity
Pages
3396-3409
Date Issued
2015
Date
2015
Author(s)
Hua, Kuo-Feng
Yang, Feng-Ling
Chiu, Hsiao-Wen
Chou, Ju-Ching
Dong, Wei-Chih
Lin, Chien-Nan
Lin, Chai-Yi
Li, Lan-Hui
Chiu, Huan-Wen
Chiu, Yi-Chich
Wu, Shih-Hsiung
McCormick, B. A.
Abstract
Klebsiella 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.
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