Properly folded and functional PorB from Neisseria gonorrhoeae inhibits dendritic cell stimulation of CD4 + T cell proliferation.

Autor:	Zhu W; From the Department of Medicine, Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina 27599., Tomberg J; the Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599., Knilans KJ; the Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599., Anderson JE; From the Department of Medicine, Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina 27599., McKinnon KP; the Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, and.; the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599., Sempowski GD; the Department of Medicine and Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710., Nicholas RA; the Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, nicholas@med.unc.edu.; the Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, and., Duncan JA; From the Department of Medicine, Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina 27599, jaduncan@med.unc.edu.; the Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599.; the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2018 Jul 13; Vol. 293 (28), pp. 11218-11229. Date of Electronic Publication: 2018 May 11.
DOI:	10.1074/jbc.RA117.001209
Abstrakt:	Neisseria gonorrhoeae is an exclusive human pathogen that evades the host immune system through multiple mechanisms. We have shown that N. gonorrhoeae suppresses the capacity of antigen-presenting cells to induce CD4 + T cell proliferation. In this study, we sought to determine the gonococcal factors involved in this adaptive immune suppression. We show that suppression of the capacity of antigen-pulsed dendritic cells to induce T cell proliferation is recapitulated by administration of a high-molecular-weight fraction of conditioned medium from N. gonorrhoeae cultures, which includes outer membrane vesicles that are shed during growth of the bacteria. N. gonorrhoeae PorB is the most abundant protein in N. gonorrhoeae -derived vesicles, and treatment of dendritic cells with purified recombinant PorB inhibited the capacity of the cells to stimulate T cell proliferation. This immunosuppressive feature of purified PorB depended on proper folding of the protein. PorB from N. gonorrhoeae , as well as other Neisseria species and other Gram-negative bacterial species, are known to activate host Toll-like receptor 2 (TLR2) signaling. Published studies have demonstrated that purified Neisseria PorB forms proteinacious nanoparticles, termed proteosomes, when detergent micelles are removed. Unlike folded, detergent-solubilized PorB, PorB proteosomes stimulate immune responses. We now demonstrate that the formation of PorB proteosomes from structurally intact PorB eliminates the immunosuppressive property of the protein while enhancing TLR2 stimulation. These findings suggest that gonococcal PorB present in shed outer membrane vesicles plays a role in suppression of adaptive immune responses to this immune-evasive pathogen. (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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