Direct stimulatory effects of the TLR2/6 ligand bacterial lipopeptide MALP-2 on neutrophil granulocytes

Med Microbiol Immunol. 2007 Jun;196(2):61-71. doi: 10.1007/s00430-006-0027-9. Epub 2006 Sep 28.

Abstract

Bacterial lipopeptides represent a group of bacterial compounds able to trigger the functions of cells of the innate immune response. Whereas diacylated lipopeptides are recognized by TLR2/6 dimers, triacylated lipopeptides were shown to act via TLR2/1 dimers. Although several previous studies dealt with the effect of the TLR2/1 ligand Pam(3)CysSK(4) on neutrophil granulocytes (PMN), it is still not clear whether TLR2/6 ligand lipopeptides can directly influence PMN functions. In the present study we used highly purified human neutrophils to investigate the direct effects of the diacylated mycoplasmal macrophage activating lipopeptide-2 (MALP-2) on the function of neutrophil granulocytes. After exposure to 10 ng/ml MALP-2 neutrophils acquired activated cell shape, secreted IL-8 and MIP-1beta and their phagocytic capacity was enhanced. Analysis of cell surface activation markers confirmed the activating effect of MALP-2, the expression of CD62L was downregulated whereas CD11b was upregulated on PMN after exposure to MALP-2. The constitutive apoptosis of PMN was inhibited after exposure to MALP-2. However, MALP-2 exerted only a short-term effect on the apoptosis of resting neutrophils, a longer lasting effect was observed after transendothelial migration. MALP-2 did not directly induce the production of reactive oxygen intermediates but primed PMN for a fMLP-induced oxidative burst. The migration of neutrophils was enhanced after treatment with MALP-2. This was due, however, to a chemokinetic rather than to a chemotactic effect. Pam(3)CysSK(4) also activated PMN, but in comparison to MALP-2, at higher concentrations. These findings suggest that diacylated lipopeptides are important microbial structures recognized by and acting on neutrophil granulocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cytokines / blood
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Humans
  • Immunity, Innate
  • Lipopeptides
  • Neutrophil Activation / drug effects*
  • Neutrophil Activation / immunology
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Oligopeptides / immunology
  • Oligopeptides / metabolism*
  • Phagocytosis / immunology
  • Respiratory Burst / physiology
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 6 / immunology
  • Toll-Like Receptor 6 / metabolism*

Substances

  • Cytokines
  • Lipopeptides
  • Oligopeptides
  • Toll-Like Receptor 2
  • Toll-Like Receptor 6
  • macrophage stimulatory lipopeptide 2