Capsular Polysaccharide Is Involved in NLRP3 Inflammasome Activation by Klebsiella pneumoniae Serotype K1

• Published in: Infection and immunity Vol. 83; no. 9; pp. 3396 - 3409
• Main Authors: Hua, Kuo-Feng, Yang, Feng-Ling, Chiu, Hsiao-Wen, Chou, Ju-Ching, Dong, Wei-Chih, Lin, Chien-Nan, Lin, Chai-Yi, Wang, Jin-Town, Li, Lan-Hui, Chiu, Huan-Wen, Chiu, Yi-Chich, Wu, Shih-Hsiung
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.09.2015
• Subjects: Animals; Antigens, Bacterial - immunology; Blotting, Western; Carrier Proteins - immunology; Cell Line; Enzyme-Linked Immunosorbent Assay; Host Response and Inflammation; Host-Parasite Interactions - immunology; Humans; Inflammasomes - immunology; Interleukin-1beta - immunology; Klebsiella Infections - immunology; Klebsiella pneumoniae - immunology; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Polysaccharides, Bacterial - immunology; Real-Time Polymerase Chain Reaction
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00125-15

Klebsiella pneumoniae (strain 43816, K2 serotype) induces interleukin-1β (IL-1β) 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-1β 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-κB activation. Inhibition of both the mitochondrial membrane permeability transition and mitochondrial ROS generation inhibited K1-CPS-mediated NLRP3 inflammasome activation. Furthermore, IL-1β 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-1β 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-1β secretion through the NLRP3 inflammasome.