The TLR2 agonists lipoteichoic acid and Pam3CSK4 induce greater pro-inflammatory responses than inactivated Mycobacterium butyricum

Cell Immunol. 2012 Nov;280(1):101-7. doi: 10.1016/j.cellimm.2012.12.001. Epub 2012 Dec 19.


The innate immune system can recognize pathogen-associated molecular patterns (PAMP) through toll-like receptors (TLRs). TLR stimulation by TLR-ligands (TLR-L) induces several genes that can regulate the immune response. In this study, we compared the ability of diverse TLR2-L to activate professional antigen presenting cells (pAPCs). We found that in comparison to whole non-replicating microorganism Mycobacterium butyricum, the smaller components; lipoteichoic acid and Pam3CSK4 significantly enhanced the expression of several pro-inflammatory mediators. These included IL-6, TNF-α and nitric oxide both at the mRNA and the protein levels. Moreover, the higher response was associated with a differential activation of nuclear transcription factor kappa-B (NF-κB) by the diverse TLR2-L. However, all three ligands enhanced antigen cross-presentation and T cell induction after virus infection to the same extent. In conclusion, the data highlight the potential for small components of TLR agonists to induce superior inflammatory immune responses than whole microbial preparation in the field of vaccine studies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / drug effects
  • Antigen-Presenting Cells / drug effects*
  • Antigen-Presenting Cells / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Cell Line, Tumor
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Gene Expression Regulation / drug effects
  • HEK293 Cells
  • Humans
  • Inflammation / chemically induced*
  • Inflammation / microbiology
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Lipopeptides / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Lymphocyte Activation / drug effects
  • Macrophages / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium / immunology*
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Teichoic Acids / pharmacology*
  • Toll-Like Receptor 2 / agonists*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics


  • Interleukin-6
  • Lipopeptides
  • Lipopolysaccharides
  • NF-kappa B
  • Pam(3)CSK(4) peptide
  • Teichoic Acids
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Nitric Oxide
  • lipoteichoic acid