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The immunomodulatory Pseudomonas aeruginosa signalling molecule N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) enters mammalian cells in an unregulated fashion

journal contribution
posted on 2023-05-17, 08:00 authored by Ritchie, AJ, Whittall, C, Lazenby, JJ, Chhabra, SR, Pritchard, DI, Cooley, MA
The Pseudomonas aeruginosa quorum-sensing signal molecule N-3-oxododecanoyl)-L-homoserine lactone (OdDHL) has been reported to affect the function of a wide range of mammalian cell types, including cells of the immune system. In T cells, it has been reported to inhibit the production of most cytokines, and it has been reported to inhibit the function of antigen-presenting cells. The intracellular target of OdDHL in these cells remains to be identified, although the lipophilic nature of the molecule suggested that the target could be membrane associated. We explored the association of radiolabelled OdDHL with the membrane and cytoplasm of Jurkat T-cell lines and of primary murine T cells and dendritic cells. We found that not only did 3H-OdDHL enter the cytoplasm of Jurkat cells without disproportionate association with the cell membrane, it also reached maximum levels in the cytoplasm very quickly, and that the intracellular concentration was proportional to the extracellular concentration. Similar results were obtained when 3H-OdDHL was incubated with primary murine T cells or cultured dendritic cells. In addition, we show that the cellular distribution of OdDHL does not significantly alter after stimulation of Jurkat cells or primary murine CD4 T cells with immobilized anti-CD3, with little activity being associated with nuclear fractions. Together, these data strongly suggest that OdDHL enters mammalian cells by passive mechanisms, and that it does not preferentially associate with the membrane or nucleus upon T-cell receptor ligation. © 2007 Australasian Society for Immunology Inc. All rights reserved.

History

Publication title

Immunology and Cell Biology

Volume

85

Issue

8

Pagination

596-602

ISSN

0818-9641

Department/School

Tasmanian School of Medicine

Publisher

Blackwell Publishing Asia

Place of publication

54 University St, P O Box 378, Carlton, Australia, Victoria, 3053

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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