Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells
Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Frontiers Media
2010
|
| Subjects: |
| _version_ | 1825720483703685120 |
|---|---|
| author | Ellegard, Rada Khalid, Mohammad Svanberg, Cecilia Holgersson, Hanna Thorén, Ylva Wittgren, Mirja Karolina Hinkula, Jorma Nyström, Sofia Shankar, Esaki Muthu Larsson, Marie |
| author_facet | Ellegard, Rada Khalid, Mohammad Svanberg, Cecilia Holgersson, Hanna Thorén, Ylva Wittgren, Mirja Karolina Hinkula, Jorma Nyström, Sofia Shankar, Esaki Muthu Larsson, Marie |
| author_sort | Ellegard, Rada |
| collection | UM |
| description | Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction. Our results showed that DCs exposed to complement-opsonized HIV (C-HIV) were less mature and had a poor ability to trigger IFN-driven NK cell activation. In addition, when the DCs were exposed to C-HIV, the cytotolytic potentials of both NK cells and CD8 T cells were markedly suppressed. The expression of PD-1 as well as co-expression of negative immune checkpoints TIM-3 and LAG-3 on PD-1 positive cells were increased on both CD4 as well as CD8 T cells upon interaction with and priming by NK-DC cross talk cultures exposed to C-HIV. In addition, stimulation by NK-DC cross talk cultures exposed to C-HIV led to the upregulation of CD38, CXCR3, and CCR4 on T cells. Together, the immune modulation induced during the presence of complement on viral surfaces is likely to favor HIV establishment, dissemination, and viral pathogenesis. |
| first_indexed | 2024-03-06T05:35:50Z |
| format | Article |
| id | um.eprints-14213 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:35:50Z |
| publishDate | 2010 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | um.eprints-142132019-08-28T03:36:36Z http://eprints.um.edu.my/14213/ Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells Ellegard, Rada Khalid, Mohammad Svanberg, Cecilia Holgersson, Hanna Thorén, Ylva Wittgren, Mirja Karolina Hinkula, Jorma Nyström, Sofia Shankar, Esaki Muthu Larsson, Marie R Medicine Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction. Our results showed that DCs exposed to complement-opsonized HIV (C-HIV) were less mature and had a poor ability to trigger IFN-driven NK cell activation. In addition, when the DCs were exposed to C-HIV, the cytotolytic potentials of both NK cells and CD8 T cells were markedly suppressed. The expression of PD-1 as well as co-expression of negative immune checkpoints TIM-3 and LAG-3 on PD-1 positive cells were increased on both CD4 as well as CD8 T cells upon interaction with and priming by NK-DC cross talk cultures exposed to C-HIV. In addition, stimulation by NK-DC cross talk cultures exposed to C-HIV led to the upregulation of CD38, CXCR3, and CCR4 on T cells. Together, the immune modulation induced during the presence of complement on viral surfaces is likely to favor HIV establishment, dissemination, and viral pathogenesis. Frontiers Media 2010 Article PeerReviewed Ellegard, Rada and Khalid, Mohammad and Svanberg, Cecilia and Holgersson, Hanna and Thorén, Ylva and Wittgren, Mirja Karolina and Hinkula, Jorma and Nyström, Sofia and Shankar, Esaki Muthu and Larsson, Marie (2010) Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells. Frontiers in Immunology, 9. p. 899. ISSN 1664-3224, DOI https://doi.org/10.3389/fimmu.2018.00899 <https://doi.org/10.3389/fimmu.2018.00899>. https://doi.org/10.3389/fimmu.2018.00899 doi:10.3389/fimmu.2018.00899 |
| spellingShingle | R Medicine Ellegard, Rada Khalid, Mohammad Svanberg, Cecilia Holgersson, Hanna Thorén, Ylva Wittgren, Mirja Karolina Hinkula, Jorma Nyström, Sofia Shankar, Esaki Muthu Larsson, Marie Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells |
| title | Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells |
| title_full | Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells |
| title_fullStr | Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells |
| title_full_unstemmed | Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells |
| title_short | Complement-opsonized HIV-1 alters cross talk between dendritic cells and natural killer (NK) cells to inhibit NK killing and to upregulate PD-1, CXCR3, and CCR4 on T cells |
| title_sort | complement opsonized hiv 1 alters cross talk between dendritic cells and natural killer nk cells to inhibit nk killing and to upregulate pd 1 cxcr3 and ccr4 on t cells |
| topic | R Medicine |
| work_keys_str_mv | AT ellegardrada complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT khalidmohammad complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT svanbergcecilia complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT holgerssonhanna complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT thorenylva complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT wittgrenmirjakarolina complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT hinkulajorma complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT nystromsofia complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT shankaresakimuthu complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells AT larssonmarie complementopsonizedhiv1alterscrosstalkbetweendendriticcellsandnaturalkillernkcellstoinhibitnkkillingandtoupregulatepd1cxcr3andccr4ontcells |