70 research outputs found
Recommended from our members
Staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the Paf receptor
Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although the underlying mechanisms are poorly understood. Here, we show that S.aureus lipoteichoic acid (LTA) inhibits platelet
aggregation caused by physiological agonists and S. aureus and reduced platelet thrombus formation in vitro. The presence of D-alanine on LTA is necessary for the full inhibitory effect. Inhibition of aggregation was blocked using a monoclonal anti-platelet activating factor receptor (PafR) antibody and Ginkgolide B, a well-defined PafR antagonist, demonstrating that the LTA inhibitory signal occurs via PafR. Using a cyclic AMP (cAMP) assay and a western blot for phosphorylated VASP, we determined that cAMP levels increase upon platelet incubation with LTA, an effect which inhibits platelet activation. This was blocked when platelets were preincubated with Ginkgolide B. Furthermore, LTA reduced haemostasis in a mouse tail-bleed assay
Differences in lipopolysaccharide- and lipoteichoic acid-induced cytokine/chemokine expression
Bona Verba Viro ... Domino Paulo Draing, Hamb. Cum is in illustri Argentoratensi Licentiaturæ Gradus, Honores & Privilegia d. XII. Jan. an. N. C. M DC LXXI. solenniter capesseret : exarata a Dominis, Patronis, Fautoribus atque Amicis submisse, devote & officiosissime venerandis, colendis
Disputatio Iuridica Inauguralis De Poenitentia
Quam ... Ex Decreto & Auctoritate ... Iurisconsultorum Ordinis In Celeberrima Argentoratensium Universitate Pro Licentia Summos in Utroque Iure Honores & Privilegia Doctoralia rite consequendi Placidae Eruditorum Disquisitioni Solenniter exhibet Paulus Draing, Hamburg. Ad d. 9. Mens. Ianuar. Horis locoq[ue] consuetisNicht identisch mit VD17 1:004646D und 32:627652N (unterschiedliche Signaturformeln
Induction of IL-10-balanced immune profiles following exposure to LTA from <em>Staphylococcus epidermidis</em>.
Staphylococcus epidermidis colonises human skin without apparent inflammation, but a dominance of S. epidermidis and S. aureus is characteristic of cutaneous microbial dysbiosis in atopic dermatitis (AD). While S. aureus can trigger AD, the role of S. epidermidis is less understood. We characterised consequences of innate immune sensing of lipoteichoic acid (LTA) preparations derived from S. epidermidis (epi-LTA) or S. aureus (aureus-LTA). Therefore, dendritic cell (DC) activation and consecutive priming of antigen-specific T cells following exposure of DC to epi-LTA or aureus-LTA were investigated. Mimicking acute AD, exposure of DC to IL-4 and LTAs was analysed. Exposure to epi-LTA or aureus-LTA activated human immune cells and murine dendritic cells (DCs) via TLR2/MyD88, however, resulting in divergent immune profiles. Differences between LTAs were significant for IL-6, IL-12p40 and IL-12p70 but not for IL-10, which was best reflected by the IL-12p70-to-IL-10 ratio being IL-10-balanced for epi-LTA but pro-inflammatory for aureus-LTA. LTA-exposed DCs activated CD4+ T cells; however, while T-cell-derived IL-10 was equivalent between LTAs, IFN-γ and IL-17 were significantly higher for aureus-LTA. Mimicking acute AD by exposing DCs to IL-4 and LTAs revealed that IL-4 significantly and uniformly suppressed epi-LTA-induced cytokine production, keeping the IL-12p70-to-IL-10 ratio balanced. In contrast, exposure of DCs to aureus-LTA and IL-4 enhanced IL-12p70 but suppressed IL-10 levels, further unbalancing the IL-12p70-to-IL-10 ratio. These data demonstrate opposing immune consequences following exposure to staphylococcal LTAs. Epi-LTA induced IL-10-balanced, aureus-LTA pro-inflammatory immune profiles
Role played by Toll-like receptors 2 and 4 in lipoteichoic acid-induced lung inflammation and coagulation
BACKGROUND: The cell wall of Streptococcus pneumoniae consists of lipoteichoic acid (LTA), which is released when pneumococci are killed by either the host immune system or antibiotic treatment. Release of excessive amounts of LTA has been implicated in the toxic sequelae of severe gram-positive infection by virtue of its proinflammatory properties. Several in vitro studies have shown that LTA is recognized by Toll-like receptor (TLR) 2 and CD14. Our objective here was to investigate the inflammatory properties of S. pneumoniae LTA in vivo and the role played by TLR2, TLR4, and CD14 therein. METHODS: Wild-type (WT), TLR2 knockout (KO), TLR4 KO, TLR2x4 double-KO, and CD14 KO mice were intranasally inoculated with highly purified pneumococcal LTA. RESULTS: LTA induced a dose-dependent inflammatory response and activation of the coagulation and fibrinolytic pathways in a TLR2-dependent fashion. Surprisingly, TLR4 KO mice also displayed a somewhat diminished pulmonary inflammatory and coagulant response compared with WT mice, possibly as a result of absent TLR4 signaling through LTA-induced release of endogenous mediators. CONCLUSION: Pneumococcal LTA induces a profound inflammatory response and activation of the coagulation pathway in the lungs in vivo through a TLR2-dependent route, which likely is amplified by endogenous TLR4 ligand
Comparison of Lipoteichoic Acid from Different Serotypes of Streptococcus pneumoniae
Pneumococcal lipoteichoic acid (LTA) is known to have a completely different chemical structure compared with that of Staphylococcus aureus: the polyglycerophosphate in the backbone is replaced in the pneumococcal LTA by a pentamer repeating unit consisting of one ribitol and a tetrasaccharide carrying the unusual substituents phosphocholine andN-acetyl-D-galactosamine. NeitherD-alaninenorN-acetyl D-glucosamine, which play central roles in the biological activity of the staphylococcal LTA, has been reported. The extraction using butanol is more gentle compared with the previously reported chloroform-methanol extraction and results in a higher yield of LTA. We characterized the LTA of two different strains of Streptococcus pneumoniae: R6 (serotype 2) and Fp23 (serotype 4). NMR analysis confirmed the structure of LTA from R6 but showed that its ribitol carries an N-acetyl-D-galactosamine substituent. The NMRdata for the LTA from Fp23 indicate that this LTA additionally contains ribitolbound D-alanine. Dose-response curves of the two pneumococcal LTAs in human whole blood revealed that LTA from Fp23 was significantly more potent than LTA from R6 with regard to the induction of all cytokines measured (tumor necrosis factor, interleukin-1 (IL-1), IL-8, IL-10, granulocyte colony-stimulating factor, and interferon &amp;#947;). However, other characteristics, such as lack of inhibition by endotoxin-specific LAL-F, Toll-like receptor 2 and not 4 dependence, and lack of stimulation of neutrophilic granulocytes, were shared by both LTAs. This is the first report of a difference in the structure of LTA between two pneumococcal serotypes resulting in different immunostimulatory potencies
The expression and significance of IL-6 and IL-10 in the process of clinical common bacteria bloodstream infection in the mouse models analyzed by the Luminex® xMAP™ System
- …