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Infect. Immun. doi:10.1128/IAI.00222-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Neisserial outer membrane vesicles bind the co-inhibitory receptor CEACAM1 and suppress CD4⁺ T lymphocyte function

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

^* To whom correspondence should be addressed. Email: scott.gray.owen{at}utoronto.ca.

	Abstract

The pathogenic Neisseria naturally liberate outer membrane ‘blebs’ which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from N. meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the function of many of their constituent proteins remains 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 (ITIM)-containing co-inhibitory 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 was 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.

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