Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids

Int Immunopharmacol. 2009 Jan;9(1):127-33. doi: 10.1016/j.intimp.2008.10.014. Epub 2008 Nov 14.


Lipoteichoic acid (LTA) is a major immunostimulating component in the cell wall of Gram-positive bacteria as lipopolysaccharide of Gram-negative bacteria. However, LTA is expressed on not only pathogenic but also nonpathogenic Gram-positive bacteria. In order to examine whether the immunostimulating potentials of Gram-positive bacteria are correlated with their LTAs, we prepared highly pure LTAs from Staphylococcus aureus (pathogenic), Bacillus subtilis (non-pathogenic), or Lactobacillus plantarum (beneficial). When a murine macrophage cell-line, RAW 264.7, was stimulated with heat-killed bacteria, both S. aureus and B. subtilis induced nitric oxide (NO) production in a dose-dependent manner while L. plantarum showed a minimal induction. Interestingly, purified LTAs from S. aureus and B. subtilis, but not from L. plantarum, were able to induce the production of NO. The differential inflammatory potentials of LTAs coincided with their abilities to activate Toll-like receptor 2 (TLR2), which is known to recognize Gram-positive bacteria and LTA, and transcription factors NF-kappaB and AP-1. Similar results were obtained with the expression of cytokines related to inflammation by RAW 264.7 and human peripheral blood mononuclear cells as well. The ability of LTA to induce TNF-alpha and NO production was abolished when the LTAs were treated with 0.2 N NaOH. Collectively, we suggest that the immunostimulating potentials of Gram-positive bacteria differ due to their LTAs with differential potencies in the stimulation of TLR2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Bacillus subtilis / chemistry
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Electrophoretic Mobility Shift Assay
  • Gram-Positive Bacteria / chemistry*
  • Gram-Positive Bacteria / immunology*
  • Humans
  • Indicators and Reagents
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Lactobacillus plantarum / chemistry
  • Limulus Test
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / isolation & purification
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Nitric Oxide / biosynthesis
  • Staphylococcus aureus / chemistry
  • Teichoic Acids / chemistry
  • Teichoic Acids / isolation & purification
  • Teichoic Acids / pharmacology*
  • Toll-Like Receptor 2 / biosynthesis
  • Transcription Factor AP-1 / genetics
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Adjuvants, Immunologic
  • Cytokines
  • Indicators and Reagents
  • Interleukin-2 Receptor alpha Subunit
  • Lipopolysaccharides
  • Teichoic Acids
  • Toll-Like Receptor 2
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • lipoteichoic acid