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Infection and Immunity, March 2005, p. 1648-1655, Vol. 73, No. 3
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.3.1648-1655.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Pseudomonas aeruginosa Quorum-Sensing Molecule N-3-(Oxododecanoyl)-L-Homoserine Lactone Inhibits T-Cell Differentiation and Cytokine Production by a Mechanism Involving an Early Step in T-Cell Activation

A. J. Ritchie,1 A. Jansson,1,2 J. Stallberg,1 P. Nilsson,2 P. Lysaght,1 and M. A. Cooley1*

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia,1 Computational Biology, Department of Life Science, University of Skövde, Skövde, Sweden2

Received 12 July 2004/ Returned for modification 28 October 2004/ Accepted 5 November 2004

The Pseudomonas aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone (OdDHL) has been reported to have immunomodulatory activity in several systems, although the mechanism of that activity remains to be fully characterized. We demonstrate here, using a defined in vitro model of antigen responses by T-cell receptor (TCR)-transgenic mouse splenic CD4 T cells, that the effect of OdDHL on activation and cytokine production is complete within 4 h of antigen or mitogen stimulation and does not depend on the insertion of OdDHL in the cell membrane, despite a previous report that immunosuppression by homoserine lactones required a minimum acyl chain length of 11 carbons (S. R. Chhabra, C. Harty, D. S. W. Hooi, M. Daykin, B. W. Bycroft, P. Williams, and D. Pritchard, J. Med. Chem. 46:97-104, 2003). We also demonstrate that while OdDHL can have toxic effects on nonlymphoid leukocytes, it does not induce significant cell death in T cells at the concentrations (≤10 µM) used in these experiments. In addition, we show that primary and secondary antigen-specific cytokine responses are equally susceptible to inhibition by OdDHL and that the compound inhibits the differentiation of both Th1 and Th2 cells. However, the precise balance of cytokine production by CD4 T cells stimulated in the presence of OdDHL varies with both the antigen concentration and its affinity for the transgenic TCR. Thus, conflicting reports of the nature of the immunosuppression by OdDHL may be due in part to the differences in antigen affinity and concentration in different models.

* Corresponding author. Mailing address: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Phone: 61-2-93853761. Fax: 61-2-93851591. E-mail: m.cooley{at}unsw.edu.au.

Editor: F. C. Fang

Infection and Immunity, March 2005, p. 1648-1655, Vol. 73, No. 3
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.3.1648-1655.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Popat, R., Crusz, S. A., Diggle, S. P. (2008). The social behaviours of bacterial pathogens. Br Med Bull 87: 63-75 [Abstract] [Full Text]  
  • Dong, Y.-H., Wang, L.-H., Zhang, L.-H. (2007). Quorum-quenching microbial infections: mechanisms and implications. Phil Trans R Soc B 362: 1201-1211 [Abstract] [Full Text]  
  • Gould, T. A., Herman, J., Krank, J., Murphy, R. C., Churchill, M. E. A. (2006). Specificity of Acyl-Homoserine Lactone Synthases Examined by Mass Spectrometry. J. Bacteriol. 188: 773-783 [Abstract] [Full Text]  


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