Structure and Immunological Characterization of the Capsular Polysaccharide of a Pyrogenic Liver Abscess Caused by Klebsiella pneumoniae ACTIVATION OF MACROPHAGES THROUGH TOLL-LIKE RECEPTOR 4

The active components of a primary pyrogenic liver abscess (PLA) Klebsiella pneumoniae in stimulating cytokine expression in macrophages are still unclear. The capsular polysaccharide (CPS) of PLA K. pneumoniae is important in determining clinical manifestations, and we have shown that it consists of repeating units of the trisaccharide (-> 3)-beta-D-Glc-(1 -> 4)-[2,3-(S)-pyruvate]-beta-D-GlcA-(1 -> 4)-alpha-L-Fuc-(1 ->) and has the unusual feature of extensive pyruvation of glucuronic acid and acetylation of C-2-OH or C-3-OH of fucose. We demonstrated that PLAK. pneumoniae CPS induces secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by macrophages through Toll-like receptor 4 (TLR4) and that this effect was lost when pyruvation and O-acetylation were chemically destroyed. Furthermore, expression of TNF-alpha and IL-6 in PLA K. pneumoniae CPS-stimulated macrophages was shown to be regulated by the TLR4/ROS/PKC-delta/NF-kappa B, TLR4/PI3-kinase/AKT/NF-kappa B, and TLR4/MAPK signaling pathways.