Presentation of lipoteichoic acid potentiates its inflammatory activity

Abstract

Lipoteichoic acid (LTA) is a major immunostimulatory molecule in the cell wall of Gram-positive bacteria. Adhesion of LTA to a polystyrene surface drastically increased its immunostimulatory potency in human whole blood in comparison to soluble LTA, although only 1% of the LTA had bound, as determined using rhodamine-labelled LTA. The release of the proinflammatory cytokines IL-1beta, TNF and IL-6 and the chemokines IL-8 and G-CSF was increased 2- to 10-fold, but IL-10 release was unaltered. This presentation effect was not shared by lipopolysaccharide (LPS) or other toll-like receptor 2 agonists and was less pronounced in polypropylene vessels. LTA did not induce cytokine release in silicone-coated borosilicate vessels, but covalent coupling of LTA to polystyrene beads restored cytokine induction in these vessels, indicating that presentation of LTA on a surface is in fact essential for its immunostimulatory potency. This novel aspect of presentation as a factor in the recognition of LTA may reflect the physiological situation in the bacterial cell wall, where LTA is anchored in the bacterial membrane and projects through the peptidoglycan. In practical terms, contamination of medical devices with components of Gram-positive bacteria may pose an underestimated inflammatory risk.

Internalization and Coreceptor Expression Are Critical for TLR2-Mediated Recognition of Lipoteichoic Acid in Human Peripheral Blood

“…As described previously (32,33), wt-LTA-induced cytokine release was also potentiated postimmobilization, but in contrast to Δlgt-LTA, was also detected under nonimmobilizing conditions. In addition, cytokine induction by wt-LTA was less dependent on serum supplementation than Δlgt-LTA, and its recognition by TLR2-transfected HEK293 cells was independent from TLR6 and CD14 coexpression.…”

Lipoprotein Lipase and Hydrofluoric Acid Deactivate Both Bacterial Lipoproteins and Lipoteichoic Acids, but Platelet-Activating Factor-Acetylhydrolase Degrades Only Lipoteichoic Acids

“…Another study showed that lipoproteins and glycosphingolipids have the ability to enhance LTAmediated inflammation by some unknown mechanism (39). The mechanism may involve altered presentation of LTA molecules since the presentation of LTA molecules has been shown to be important (11). Thus, in actual infections with Grϩ bacteria, several additional bacterial molecules may synergize with LTA to greatly increase its inflammatory potential.…”

Staphylococcus aureuslipoteichoic acid triggers inflammation in the lactating bovine mammary gland

“…Assuming that LTA makes up about 2% of the dry cell weight [19], 20 g LTA would equate to several billion staphylocci, numbers well above the numbers found in mastitic udders. Nevertheless, LTA is likely to be of biological significance because (i) recent data indicate that the physical presentation of LTA (such as immobilization on a solid surface) increases LTA activity by several orders of magnitude [11]; and (ii) LTA can act synergistically with other PAMP, which could still lower the amount required to induce inflammation by an order of magnitude.…”