Association of Neisseria gonorrhoeae Opa(CEA) with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response.
Infection with Neisseria gonorrhoeae (N. gonorrhoeae) can trigger an intense local inflammatory response at the site of infection, yet there is little specific immune response or development of immune memory. Gonococcal surface epitopes are known to undergo antigenic variation; however, this is unli...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3570455?pdf=render |
| _version_ | 1828430799529050112 |
|---|---|
| author | Qigui Yu Edith M C Chow Shannon E McCaw Ningjie Hu Daniel Byrd Tohti Amet Sishun Hu Mario A Ostrowski Scott D Gray-Owen |
| author_facet | Qigui Yu Edith M C Chow Shannon E McCaw Ningjie Hu Daniel Byrd Tohti Amet Sishun Hu Mario A Ostrowski Scott D Gray-Owen |
| author_sort | Qigui Yu |
| collection | DOAJ |
| description | Infection with Neisseria gonorrhoeae (N. gonorrhoeae) can trigger an intense local inflammatory response at the site of infection, yet there is little specific immune response or development of immune memory. Gonococcal surface epitopes are known to undergo antigenic variation; however, this is unlikely to explain the weak immune response to infection since individuals can be re-infected by the same serotype. Previous studies have demonstrated that the colony opacity-associated (Opa) proteins on the N. gonorrhoeae surface can bind human carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) on CD4⁺ T cells to suppress T cell activation and proliferation. Interesting in this regard, N. gonorrhoeae infection is associated with impaired HIV-1 (human immunodeficiency virus type 1)-specific cytotoxic T-lymphocyte (CTL) responses and with transient increases in plasma viremia in HIV-1-infected patients, suggesting that N. gonorrhoeae may also subvert immune responses to co-pathogens. Since dendritic cells (DCs) are professional antigen presenting cells (APCs) that play a key role in the induction of an adaptive immune response, we investigated the effects of N. gonorrhoeae Opa proteins on human DC activation and function. While morphological changes reminiscent of DC maturation were evident upon N. gonorrhoeae infection, we observed a marked downregulation of DC maturation marker CD83 when the gonococci expressing CEACAM1-specific Opa(CEA), but not other Opa variants. Consistent with a gonococcal-induced defect in maturation, Opa(CEA) binding to CEACAM1 reduced the DCs' capacity to stimulate an allogeneic T cell proliferative response. Moreover, Opa(CEA)-expressing N. gonorrhoeae showed the potential to impair DC-dependent development of specific adaptive immunity, since infection with Opa(CEA)-positive gonococci suppressed the ability of DCs to stimulate HIV-1-specific memory CTL responses. These results reveal a novel mechanism to explain why infection of N. gonorrhoeae fails to trigger an effective specific immune response or develop immune memory, and may affect the potent synergy between gonorrhea and HIV-1 infection. |
| first_indexed | 2024-12-10T17:54:19Z |
| format | Article |
| id | doaj.art-16a9c2565e22427aa74c20629ab3eb58 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T17:54:19Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-16a9c2565e22427aa74c20629ab3eb582022-12-22T01:38:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5670510.1371/journal.pone.0056705Association of Neisseria gonorrhoeae Opa(CEA) with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response.Qigui YuEdith M C ChowShannon E McCawNingjie HuDaniel ByrdTohti AmetSishun HuMario A OstrowskiScott D Gray-OwenInfection with Neisseria gonorrhoeae (N. gonorrhoeae) can trigger an intense local inflammatory response at the site of infection, yet there is little specific immune response or development of immune memory. Gonococcal surface epitopes are known to undergo antigenic variation; however, this is unlikely to explain the weak immune response to infection since individuals can be re-infected by the same serotype. Previous studies have demonstrated that the colony opacity-associated (Opa) proteins on the N. gonorrhoeae surface can bind human carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) on CD4⁺ T cells to suppress T cell activation and proliferation. Interesting in this regard, N. gonorrhoeae infection is associated with impaired HIV-1 (human immunodeficiency virus type 1)-specific cytotoxic T-lymphocyte (CTL) responses and with transient increases in plasma viremia in HIV-1-infected patients, suggesting that N. gonorrhoeae may also subvert immune responses to co-pathogens. Since dendritic cells (DCs) are professional antigen presenting cells (APCs) that play a key role in the induction of an adaptive immune response, we investigated the effects of N. gonorrhoeae Opa proteins on human DC activation and function. While morphological changes reminiscent of DC maturation were evident upon N. gonorrhoeae infection, we observed a marked downregulation of DC maturation marker CD83 when the gonococci expressing CEACAM1-specific Opa(CEA), but not other Opa variants. Consistent with a gonococcal-induced defect in maturation, Opa(CEA) binding to CEACAM1 reduced the DCs' capacity to stimulate an allogeneic T cell proliferative response. Moreover, Opa(CEA)-expressing N. gonorrhoeae showed the potential to impair DC-dependent development of specific adaptive immunity, since infection with Opa(CEA)-positive gonococci suppressed the ability of DCs to stimulate HIV-1-specific memory CTL responses. These results reveal a novel mechanism to explain why infection of N. gonorrhoeae fails to trigger an effective specific immune response or develop immune memory, and may affect the potent synergy between gonorrhea and HIV-1 infection.http://europepmc.org/articles/PMC3570455?pdf=render |
| spellingShingle | Qigui Yu Edith M C Chow Shannon E McCaw Ningjie Hu Daniel Byrd Tohti Amet Sishun Hu Mario A Ostrowski Scott D Gray-Owen Association of Neisseria gonorrhoeae Opa(CEA) with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response. PLoS ONE |
| title | Association of Neisseria gonorrhoeae Opa(CEA) with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response. |
| title_full | Association of Neisseria gonorrhoeae Opa(CEA) with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response. |
| title_fullStr | Association of Neisseria gonorrhoeae Opa(CEA) with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response. |
| title_full_unstemmed | Association of Neisseria gonorrhoeae Opa(CEA) with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response. |
| title_short | Association of Neisseria gonorrhoeae Opa(CEA) with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response. |
| title_sort | association of neisseria gonorrhoeae opa cea with dendritic cells suppresses their ability to elicit an hiv 1 specific t cell memory response |
| url | http://europepmc.org/articles/PMC3570455?pdf=render |
| work_keys_str_mv | AT qiguiyu associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse AT edithmcchow associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse AT shannonemccaw associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse AT ningjiehu associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse AT danielbyrd associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse AT tohtiamet associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse AT sishunhu associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse AT marioaostrowski associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse AT scottdgrayowen associationofneisseriagonorrhoeaeopaceawithdendriticcellssuppressestheirabilitytoelicitanhiv1specifictcellmemoryresponse |