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Infection and Immunity, September 2007, p. 4449-4455, Vol. 75, No. 9
0019-9567/07/$08.00+0     doi:10.1128/IAI.00222-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4+ T Lymphocyte Function{triangledown}

Hannah S. W. Lee,1,{dagger} Ian C. Boulton,1,{dagger} Karen Reddin,2 Henry Wong,1 Denise Halliwell,2 Ofer Mandelboim,3 Andrew R. Gorringe,2 and Scott D. Gray-Owen1*

Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada,1 Health Protection Agency Centre for Emergency Preparedness and Response, Porton Down, Salisbury SP4 0JG, United Kingdom,2 The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Jerusalem, Israel3

Received 10 February 2007/ Returned for modification 22 March 2007/ Accepted 2 July 2007

Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4+ T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.

* Corresponding author. Mailing address: Department of Medical Genetics and Microbiology, University of Toronto, Room 4381, Medical Sciences Building, 1 Kings College Circle, Toronto, Ontario M5S 1A8, Canada. Phone: (416) 946-5307. Fax: (416) 978-6885. E-mail: scott.gray.owen{at}utoronto.ca

{triangledown} Published ahead of print on 9 July 2007.

Editor: J. N. Weiser

{dagger} These authors contributed equally to this work.

Infection and Immunity, September 2007, p. 4449-4455, Vol. 75, No. 9
0019-9567/07/$08.00+0     doi:10.1128/IAI.00222-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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