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Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes

Abstract

Infection with Neisseria gonorrhoeae can trigger an intense inflammatory response, yet there is little specific immune response or development of immune memory. In addition, gonorrhea typically correlates with a transient reduction in T lymphocyte counts in blood, and these populations recover when gonococcal infection is resolved. Such observations suggest that the gonococci have a suppressive effect on the host immune response. We report here that N. gonorrhoeae Opa proteins were able to bind CEACAM1 expressed by primary CD4+ T lymphocytes and suppress their activation and proliferation. CEACAM1 bound by gonococcal Opa52 associated with the tyrosine phosphatases SHP-1 and SHP-2, which implicates the receptor's ITIM (immunoreceptor tyrosine-based inhibitory motif) in this effect.

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Figure 1: Determination of CEACAM1 expression and surface exposure in primary CD4+ T lymphocytes.
Figure 2: Determination of CD69 surface expression by primary CD4+ T lymphocytes.
Figure 3: Effect of CEACAM1 ligation on IL-2–dependent proliferation of primary CD4+ T lymphocytes.
Figure 4: Influence of CEACAM1 ligation on the proliferation of primary CD4+ T lymphocytes.
Figure 5: Characterization and quantification of cell death in primary CD4+ T lymphocytes.
Figure 6: SHP-1 and SHP-2 tyrosine phosphatases associate with CEACAM1 that is bound by Opa52-expressing N. gonorrhoeae.

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Acknowledgements

We thank E. M. Bertram, J. Cannons, A. Cochrane, H. Ginzberg, K. Ireton, M. Luscher, E. Liao, S. E. McCaw, K. McDonald, M. Ostrowski and T. Watts for critical comments on and/or technical assistance. Supported by the Canadian Institutes for Health Research Operating Grant # MT-15499.

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Correspondence to Scott D. Gray-Owen.

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C. B. and S. D. G.-O. have filed a US provisional patent application entitled “Ligation of CEACAM1”, which describes the ability of CEACAM1 ligation to modulate immune cell responses and the potential applications of this effect.

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Boulton, I., Gray-Owen, S. Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes. Nat Immunol 3, 229–236 (2002). https://doi.org/10.1038/ni769

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