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

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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 Pam3CysSK4 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-1β 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. Pam3CysSK4 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.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgesellschaft (La1267/1–2; SFB 367/B10) and from the Medical Faculty of the University of Luebeck (SP Infektabwehr/B1). The authors thank Dr. Ulrich Zähringer, Dr. Norbert Reiling and Ms. Uta Bussmeyer for fruitful discussions and Ms. Kirsten Broszat for expert technical assistance.

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  1. Institute of Medical Microbiology and Hygiene, University of Luebeck, Ratzeburger Allee 160, 23538, Lubeck, Germany

    Inga Wilde, Sonja Lotz, David Engelmann, Andrea Starke, Ger van Zandbergen, Werner Solbach & Tamás Laskay

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  1. Inga Wilde
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  2. Sonja Lotz
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  3. David Engelmann
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Correspondence to Tamás Laskay.

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Wilde, I., Lotz, S., Engelmann, D. et al. Direct stimulatory effects of the TLR2/6 ligand bacterial lipopeptide MALP-2 on neutrophil granulocytes. Med Microbiol Immunol 196, 61–71 (2007). https://doi.org/10.1007/s00430-006-0027-9

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  • DOI: https://doi.org/10.1007/s00430-006-0027-9

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