SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression
HLA-E expression plays a central role for modulation of NK cell function by interaction with inhibitory NKG2A and stimulatory NKG2C receptors on canonical and adaptive NK cells, respectively. Here, we demonstrate that infection of human primary lung tissue with SARS-CoV-2 leads to increased HLA-E ex...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2361019 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846138690673311744 |
|---|---|
| author | Mohammad Zahidul Hasan Maren Claus Nadine Krüger Sarah Reusing Eline Gall Christina Bade-Döding Armin Braun Carsten Watzl Markus Uhrberg Lutz Walter |
| author_facet | Mohammad Zahidul Hasan Maren Claus Nadine Krüger Sarah Reusing Eline Gall Christina Bade-Döding Armin Braun Carsten Watzl Markus Uhrberg Lutz Walter |
| author_sort | Mohammad Zahidul Hasan |
| collection | DOAJ |
| description | HLA-E expression plays a central role for modulation of NK cell function by interaction with inhibitory NKG2A and stimulatory NKG2C receptors on canonical and adaptive NK cells, respectively. Here, we demonstrate that infection of human primary lung tissue with SARS-CoV-2 leads to increased HLA-E expression and show that processing of the peptide YLQPRTFLL from the spike protein is primarily responsible for the strong, dose-dependent increase of HLA-E. Targeting the peptide site within the spike protein revealed that a single point mutation was sufficient to abrogate the increase in HLA-E expression. Spike-mediated induction of HLA-E differentially affected NK cell function: whereas degranulation, IFN-γ production, and target cell cytotoxicity were enhanced in NKG2C+ adaptive NK cells, effector functions were inhibited in NKG2A+ canonical NK cells. Analysis of a cohort of COVID-19 patients in the acute phase of infection revealed that adaptive NK cells were induced irrespective of the HCMV status, challenging the paradigm that adaptive NK cells are only generated during HCMV infection. During the first week of hospitalization, patients exhibited a selective increase of early NKG2C+CD57− adaptive NK cells whereas mature NKG2C+CD57+ cells remained unchanged. Further analysis of recovered patients suggested that the adaptive NK cell response is primarily driven by a wave of early adaptive NK cells during acute infection that wanes once the infection is cleared. Together, this study suggests that NK cell responses to SARS-CoV-2 infection are majorly influenced by the balance between canonical and adaptive NK cells via the HLA-E/NKG2A/C axis. |
| format | Article |
| id | doaj-art-922fdbe1e53a41a29cccf93946fdf801 |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-922fdbe1e53a41a29cccf93946fdf8012024-12-07T04:40:17ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2361019SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expressionMohammad Zahidul Hasan0Maren Claus1Nadine Krüger2Sarah Reusing3Eline Gall4Christina Bade-Döding5Armin Braun6Carsten Watzl7Markus Uhrberg8Lutz Walter9Primate Genetics Laboratory, German Primate Center, Leibniz-Institute for Primate Research, Göttingen, GermanyDepartment for Immunology, Leibniz Research Centre for Working Environment and Human Factors (IfADo) at TU Dortmund, Dortmund, GermanyPlatform Infection Models, German Primate Center, Leibniz-Institute for Primate Research, Göttingen, GermanyInstitute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, GermanyInstitute for Transfusion Medicine, Hannover Medical School, Hannover, GermanyInstitute for Transfusion Medicine, Hannover Medical School, Hannover, GermanyFraunhofer Institute for Toxicology and Experimental Medicine, Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Hannover, GermanyDepartment for Immunology, Leibniz Research Centre for Working Environment and Human Factors (IfADo) at TU Dortmund, Dortmund, GermanyInstitute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, GermanyPrimate Genetics Laboratory, German Primate Center, Leibniz-Institute for Primate Research, Göttingen, GermanyHLA-E expression plays a central role for modulation of NK cell function by interaction with inhibitory NKG2A and stimulatory NKG2C receptors on canonical and adaptive NK cells, respectively. Here, we demonstrate that infection of human primary lung tissue with SARS-CoV-2 leads to increased HLA-E expression and show that processing of the peptide YLQPRTFLL from the spike protein is primarily responsible for the strong, dose-dependent increase of HLA-E. Targeting the peptide site within the spike protein revealed that a single point mutation was sufficient to abrogate the increase in HLA-E expression. Spike-mediated induction of HLA-E differentially affected NK cell function: whereas degranulation, IFN-γ production, and target cell cytotoxicity were enhanced in NKG2C+ adaptive NK cells, effector functions were inhibited in NKG2A+ canonical NK cells. Analysis of a cohort of COVID-19 patients in the acute phase of infection revealed that adaptive NK cells were induced irrespective of the HCMV status, challenging the paradigm that adaptive NK cells are only generated during HCMV infection. During the first week of hospitalization, patients exhibited a selective increase of early NKG2C+CD57− adaptive NK cells whereas mature NKG2C+CD57+ cells remained unchanged. Further analysis of recovered patients suggested that the adaptive NK cell response is primarily driven by a wave of early adaptive NK cells during acute infection that wanes once the infection is cleared. Together, this study suggests that NK cell responses to SARS-CoV-2 infection are majorly influenced by the balance between canonical and adaptive NK cells via the HLA-E/NKG2A/C axis.https://www.tandfonline.com/doi/10.1080/22221751.2024.2361019SARS-CoV-2 infectionadaptive NK cellsHLAENKG2ANKG2C |
| spellingShingle | Mohammad Zahidul Hasan Maren Claus Nadine Krüger Sarah Reusing Eline Gall Christina Bade-Döding Armin Braun Carsten Watzl Markus Uhrberg Lutz Walter SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression Emerging Microbes and Infections SARS-CoV-2 infection adaptive NK cells HLAE NKG2A NKG2C |
| title | SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression |
| title_full | SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression |
| title_fullStr | SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression |
| title_full_unstemmed | SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression |
| title_short | SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression |
| title_sort | sars cov 2 infection induces adaptive nk cell responses by spike protein mediated induction of hla e expression |
| topic | SARS-CoV-2 infection adaptive NK cells HLAE NKG2A NKG2C |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2361019 |
| work_keys_str_mv | AT mohammadzahidulhasan sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT marenclaus sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT nadinekruger sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT sarahreusing sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT elinegall sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT christinabadedoding sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT arminbraun sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT carstenwatzl sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT markusuhrberg sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression AT lutzwalter sarscov2infectioninducesadaptivenkcellresponsesbyspikeproteinmediatedinductionofhlaeexpression |