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The P.aeruginosa quorum sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone (OdDHL) inhibits T cell differentiation and cytokine production by a mechanism involving an early step in T cell activation

Citation

Ritchie, AJ and Jansson, A and Stallberg, J and Nilsson, P and Lysaght, P and Cooley, MA, The P.aeruginosa quorum sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone (OdDHL) inhibits T cell differentiation and cytokine production by a mechanism involving an early step in T cell activation, Infection and Immunity, 73, (3) pp. 1648-1655. ISSN 0019-9567 (2005) [Refereed Article]

DOI: doi:10.1128/IAI.73.3.1648-1655.2005

Abstract

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. Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Cooley, MA (Associate Professor Margaret Cooley)
ID Code:72727
Year Published:2005
Web of Science® Times Cited:57
Deposited By:Medicine (Discipline)
Deposited On:2011-08-31
Last Modified:2011-08-31
Downloads:0

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