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Neisseria gonorrhoeae suppresses dendritic cell-induced, antigen-dependent CD4 T cell proliferation.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (7), pp. e41260. Date of Electronic Publication: 2012 Jul 23. - Publication Year :
- 2012
-
Abstract
- Neisseria gonorrhoeae is the second most common sexually transmitted bacterial pathogen worldwide. Diseases associated with N. gonorrhoeae cause localized inflammation of the urethra and cervix. Despite this inflammatory response, infected individuals do not develop protective adaptive immune responses to N. gonorrhoeae. N. gonorrhoeae is a highly adapted pathogen that has acquired multiple mechanisms to evade its host's immune system, including the ability to manipulate multiple immune signaling pathways. N. gonorrhoeae has previously been shown to engage immunosuppressive signaling pathways in B and T lymphocytes. We have now found that N. gonorrhoeae also suppresses adaptive immune responses through effects on antigen presenting cells. Using primary, murine bone marrow-derived dendritic cells and lymphocytes, we show that N. gonorrhoeae-exposed dendritic cells fail to elicit antigen-induced CD4+ T lymphocyte proliferation. N. gonorrhoeae exposure leads to upregulation of a number of secreted and dendritic cell surface proteins with immunosuppressive properties, particularly Interleukin 10 (IL-10) and Programmed Death Ligand 1 (PD-L1). We also show that N. gonorrhoeae is able to inhibit dendritic cell- induced proliferation of human T-cells and that human dendritic cells upregulate similar immunosuppressive molecules. Our data suggest that, in addition to being able to directly influence host lymphocytes, N. gonorrhoeae also suppresses development of adaptive immune responses through interactions with host antigen presenting cells. These findings suggest that gonococcal factors involved in host immune suppression may be useful targets in developing vaccines that induce protective adaptive immune responses to this pathogen.
- Subjects :
- Adaptive Immunity immunology
Animals
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
Cell Proliferation
Cytokines metabolism
Dendritic Cells cytology
Dendritic Cells metabolism
Gene Expression Regulation immunology
Humans
Mice
Signal Transduction immunology
Antigens, Bacterial immunology
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes microbiology
Dendritic Cells immunology
Dendritic Cells microbiology
Immune Tolerance immunology
Neisseria gonorrhoeae immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22844448
- Full Text :
- https://doi.org/10.1371/journal.pone.0041260