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. 2007 Sep;75(9):4449-55.
doi: 10.1128/IAI.00222-07. Epub 2007 Jul 9.

"V体育ios版" Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function

Hannah S W Lee  1 , Ian C Boulton, Karen Reddin, Henry Wong, Denise Halliwell, Ofer Mandelboim, Andrew R Gorringe, Scott D Gray-Owen
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Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function

"VSports在线直播" Hannah S W Lee et al. Infect Immun. 2007 Sep.

Abstract

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 VSports手机版. .

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Figures

FIG. 1.
FIG. 1.
Expression and binding pattern of Opa proteins found on neisserial OMVs. A transmission electron micrograph illustrating intact diplococci and isolated OMVs is shown. N. meningitidis (A) and N. lactamica (B) each have closely associated naturally occurring membrane “blebs” (filled arrows) as well as others liberated from the bacteria. (C) Immunoblot probed using Opa protein-specific monoclonal antibody illustrating the presence of an Opa variant in Nm-OMVs but not in comparable Nl-OMVs as well as in OMVs derived from isogenic N. gonorrhoeae strains expressing either the CEACAM receptor-specific Opa (OpaCCM) or the HSPG receptor-specific Opa (OpaHSPG) protein but not in the strain expressing no Opa protein [Opa(−)]. (D) ELISA quantifying interactions between neisserial OMVs (10 μg total protein per well) and soluble CEACAM1-Fc. OMVs containing Opa variants that bind CEACAM1 are indicated with black bars. Relative binding was calculated based upon mean values for wells incubated with N. meningitidis-derived OMVs versus those for wells with no OMV, being 100 and 0%, respectively. In each instance, error bars indicate the standard deviations based upon values from three replicate wells. (E) Flow cytometry analysis of the association between FITC-labeled OMVs and IL-2-prestimulated lymphocytes. Matched cell populations were prestimulated using IL-2 and then incubated in the presence of FITC-OMVs derived from N. gonorrhoeae expressing the indicated Opa variants. Markers delineate the regions containing peak fluorescence intensities for T cells incubated with OMVs from OpaHSPG-expressing bacteria, drawn for comparative purposes.
FIG. 2.
FIG. 2.
Proliferation of CD4+ T lymphocytes in response to CEACAM1 ligation by neisserial OMVs or antibody. Primary CD4+ T cells were cultured in the presence of IL-2 and cross-linked CD3ɛ- and CD28-specific antibodies with various protein concentrations of either Nl-OMVs (gray bars) or Nm-OMVs (black bars) (A) or CEACAM-specific antisera (black bars) or nonreactive isotype control antibodies (gray bars) or no additions (white bars) (B). The calculated increase in culture density is relative to the number of cells present at the onset of the experiment (time = 0 h). In each instance, error bars indicate the standard deviations based upon values from six replicate samples, with results being representative of three independent experiments. Asterisks indicate P values of <0.01 for comparison with Nl-OMVs (A) or isotype control antibodies (B).
FIG. 3.
FIG. 3.
Proliferation and CD69 expression of CD4+ T lymphocytes in response to CEACAM1 binding by Opa-specific neisserial OMVs. Jurkat CD4+ T cells were cultured in the presence of IL-2 and/or cross-linked CD3ɛ-specific antibodies with OMVs (50 μg/ml protein) prepared from N. gonorrhoeae-expressing defined Opa variants. OMVs that bind CEACAM1 are indicated with black bars. (A) The mean increase in relative culture density was calculated relative to the number of cells in uninfected samples, which was defined as 100%. Error bars indicate the standard deviations based upon values from six quadrants counted for each sample. (B) The proportion of cells expressing the early activation marker CD69 16 h following the onset of the experiment was determined by flow cytometry, with standard deviation calculations based upon three independent samples. Asterisks indicate P values of <0.0002 (A) or <0.005 (B) for comparison with the other OMV-treated samples in each set.
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References

    1. Aase, A., L. M. Naess, R. H. Sandin, T. K. Herstad, F. Oftung, J. Holst, I. L. Haugen, E. A. Hoiby, and T. E. Michaelsen. 2003. Comparison of functional immune responses in humans after intranasal and intramuscular immunisations with outer membrane vesicle vaccines against group B meningococcal disease. Vaccine 21:2042-2051. - PubMed
    1. Achtman, M., M. Neibert, B. A. Crowe, W. Strittmatter, B. Kusecek, E. Weyse, M. J. Walsh, B. Slawig, G. Morelli, A. Moll, and M. Blake. 1988. Purification and characterization of eight class 5 outer membrane protein variants from a clone of Neisseria meningitidis serogroup A. J. Exp. Med. 168:507-525. - PMC - PubMed
    1. Bhat, K. S., C. P. Gibbs, O. Barrera, S. G. Morrison, F. Jahnig, A. Stern, E. M. Kupsch, T. F. Meyer, and J. Swanson. 1991. The opacity proteins of Neisseria gonorrhoeae strain MS11 are encoded by a family of 11 complete genes. Mol. Microbiol. 5:1889-1901. (Erratum, 6:1073-1076.) - "V体育官网入口" PubMed
    1. Bjune, G., E. A. Hoiby, J. K. Gronnesby, O. Arnesen, J. H. Fredriksen, A. Halstensen, E. Holten, A. K. Lindbak, H. Nokleby, and E. Rosenqvist. 1991. Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet 338:1093-1096. - PubMed
    1. Boulton, I. C., and S. D. Gray-Owen. 2002. Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes. Nat. Immunol. 3:229-236. - PubMed

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