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Infection and Immunity, November 2009, p. 5170-5180, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00355-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Opa⁺ and Opa^– Isolates of Neisseria meningitidis and Neisseria gonorrhoeae Induce Sustained Proliferative Responses in Human CD4⁺ T Cells ^,

Abdel-Rahman Youssef,¹ Michiel van der Flier,^2,3 Silvia Estevão,³ Nico G. Hartwig,^2,3 Peter van der Ley,⁴ and Mumtaz Virji^1*

Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom,¹ Department of Pediatric Infectious Diseases and Immunology,² Laboratory of Pediatrics, Pediatric Infectious Diseases, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands,³ Netherlands Vaccine Institute, Bilthoven, The Netherlands⁴

Received 26 March 2009/ Returned for modification 5 June 2009/ Accepted 24 August 2009

T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses. Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed on activated T cells. Since CEACAM1 can act as an inhibitory receptor and T cells in subepithelial tissues may encounter whole bacteria, which often express Opa proteins in vivo, this study assessed primarily if Opa proteins expressed on meningococci affect T-cell functions. In addition, Opa-containing outer membrane vesicles (OMV) have been used as vaccine antigens, and therefore Opa⁺ and Opa^– OMV were also studied. While Opa⁺ bacteria adhered to CEACAM-expressing T cells, both the Opa⁺ and Opa^– phenotypes induced no to a small transient depression, followed by a prolonged increase in proliferation as well as cytokine production. Such responses were also observed with heat-killed bacteria or OMV. In addition, while anti-CEACAM antibodies alone inhibited proliferation, on coincubation of T cells with bacteria and the antibodies, bacterial effects predominated and were Opa independent. Thus, while Opa proteins of N. meningitidis can bind to T-cell-expressed CEACAM1, this is not sufficient to overcome the T-cell recognition of bacterial factors, which results in a proliferative and cytokine response, an observation consistent with the ability of the host to establish lasting immunity to Opa-expressing meningococci that it frequently encounters. The data also imply that Opa-proficient vaccine preparations may not necessarily inhibit T-cell functions via CEACAM1 binding.

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* Corresponding author. Mailing address: Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom. Phone and fax: 44 117 331 2035. E-mail: m.virji{at}bristol.ac.uk

Published ahead of print on 31 August 2009.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. N. Weiser

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Infection and Immunity, November 2009, p. 5170-5180, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00355-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.