Opa(+) and Opa(-) Isolates of Neisseria meningitidis and Neisseria gonorrhoeae Induce Sustained Proliferative Responses in Human CD4(+) T Cells

Abdel Rahman Youssef, Michiel van der Flier, Silvia Estevao, Nico G. Hartwig, Peter van der Ley, Mumtaz Virji*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

21 Citations (Scopus)

Abstract

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.

Translated title of the contributionOpa(+) and Opa(-) isolates of Neisseria meningitidis and Neisseria gonorrhoeae induce sustained proliferative responses in human CD4(+) T cells
Original languageEnglish
Pages (from-to)5170-5180
Number of pages11
JournalInfection and Immunity
Volume77
Issue number11
DOIs
Publication statusPublished - Nov 2009

Keywords

  • CARCINOEMBRYONIC ANTIGEN FAMILY
  • CELLULAR ADHESION MOLECULE-1
  • OUTER-MEMBRANE PROTEINS
  • ENDOTHELIAL-CELLS
  • EPITHELIAL-CELLS
  • CRITICAL DETERMINANTS
  • MENINGOCOCCAL OPA
  • PERIPHERAL-BLOOD
  • OPACITY PROTEINS
  • N-DOMAIN

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