Teichoic Acids Are Not Required forStreptococcus pneumoniaeandStaphylococcus aureusCell Walls To Trigger the Release of Tumor Necrosis Factor by Peripheral Blood Monocytes

Abstract

In gram-negative bacteria, the outer membrane lipopolysaccharide is the main component triggering cytokine release from peripheral blood mononuclear cells (PBMCs). In gram-positive bacteria, purified walls also induce cytokine release, but stimulation requires 100 times more material. Gram-positive walls are complex megamolecules reassembling distinct structures. Only some of them might be inflammatory, whereas others are not. Teichoic acids (TA) are an important portion (>50%) of gram-positive walls. TA directly interact with C3b of complement and the cellular receptor for platelet-activating factor. However, their contribution to wall-induced cytokine-release by PBMCs has not been studied in much detail. In contrast, their membranebound lipoteichoic acids (LTA) counterparts were shown to trigger inflammation and synergize with peptidoglycan (PGN) for releasing nitric oxide (NO). This raised the question as to whether TA are also inflammatory. We determined the release of tumor necrosis factor (TNF) by PBMCs exposed to a variety of TA-rich and TAfree wall fragments from Streptocccus pneumoniae and Staphylococcus aureus. TA-rich walls from both organisms induced measurable TNF release at concentrations of 1 g/ml. Removal of wall-attached TA did not alter this activity. Moreover, purified pneumococcal and staphylococcal TA did not trigger TNF release at concentrations as high as >100 g/ml. In contrast, purified LTA triggered TNF release at 1 g/ml. PGN-stem peptide oligomers lacking TA or amino-sugars were highly active and triggered TNF release at concentrations as low as 0.01 g/ml (P. A. Majcherczyk, H. Langen, et al., J. Biol. Chem. 274:12537-12543,1999). Thus, although TA is an important part of gram-positive walls, it did not participate to the TNF-releasing activity of PGN.

The discriminatory power of MALDI-TOF mass spectrometry to differentiate between isogenic teicoplanin-susceptible and teicoplanin-resistant strains of methicillin-resistantStaphylococcus aureus

“…Insoluble peptidoglycan was purified from cultures grown to mid-log phase in brain heart infusion broth using a previously described standard procedure (de Jonge et al, 1992;Majcherczyk et al, 2003). After removal of teichoic acids by hydrofluoric acid insoluble peptidoglycan was digested with muramidase, yielding soluble muropeptides (de Jonge et al, 1992).…”

Recognition ofStaphylococcus aureusby the Innate Immune System

“…Although crucial for bacterial life, purified wall teichoic acids of S. aureus are not very inflammatory (108). However, a number of studies suggest that the bacterial LTA of S. aureus may contribute to sepsis (83).…”

Trovafloxacin Enhances the Inflammatory Response to a Gram-Negative or a Gram-Positive Bacterial Stimulus, Resulting in Neutrophil-Dependent Liver Injury in Mice

“…Bacterial components of both Gram-positive bacteria (peptidoglycan [PGN] and lipoteichoic acid [LTA]) and Gram-negative bacteria (lipopolysaccharide [LPS]) activate Toll-like receptors (TLRs) to induce inflammation. PGN and LTA activate TLR2 and induce NF-B activation through MyD88-dependent mechanisms (Schwandner et al, 1999;Majcherczyk et al, 2003;Moreillon and Majcherczyk, 2003;Weber et al, 2003). LPS activates TLR4 and induces NF-B activation through both MyD88-dependent and -independent mechanisms (Janssens and Beyaert, 2003).…”