Properly folded and functional PorB from Neisseria gonorrhoeae inhibits dendritic cell stimulation of CD4+ T cell proliferation
Autor: | Kayla J. Knilans, Joseph A. Duncan, James E. Anderson, Robert A. Nicholas, Karen P. McKinnon, Joshua Tomberg, Weiyan Zhu, Gregory D. Sempowski |
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Rok vydání: | 2018 |
Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Protein Folding T cell Immunology 030106 microbiology Porins Lymphocyte Activation medicine.disease_cause Biochemistry Gonorrhea 03 medical and health sciences Immune system medicine Humans Molecular Biology Cells Cultured Cell Proliferation biology Chemistry Dendritic Cells Cell Biology Dendritic cell biology.organism_classification Neisseria gonorrhoeae Toll-Like Receptor 2 Cell biology TLR2 030104 developmental biology medicine.anatomical_structure Porin Neisseria Bacterial outer membrane Signal Transduction |
Zdroj: | Journal of Biological Chemistry. 293:11218-11229 |
ISSN: | 0021-9258 |
Popis: | 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. |
Databáze: | OpenAIRE |
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