Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity
Background: Antibody-dependent cell-mediated cytotoxic (ADCC) response mediated by natural killer (NK) cells correlates with decreased infection risk in studies involving simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV), and human immunodeficiency virus (HIV) vaccine c...
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Case Western Reserve University
2025-01-01
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| Series: | Pathogens and Immunity |
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| Online Access: | https://www.paijournal.com/index.php/paijournal/article/view/734 |
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| author | Junsuke Nohara Tyler Evangelous Madison Berry Whitney Beck Sarah Mudrak Shalini Jha R. Keith Reeves Kevin J. Wiehe Justin Pollara Georgia Tomaras Todd Bradley Guido Ferrari |
| author_facet | Junsuke Nohara Tyler Evangelous Madison Berry Whitney Beck Sarah Mudrak Shalini Jha R. Keith Reeves Kevin J. Wiehe Justin Pollara Georgia Tomaras Todd Bradley Guido Ferrari |
| author_sort | Junsuke Nohara |
| collection | DOAJ |
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Background: Antibody-dependent cell-mediated cytotoxic (ADCC) response mediated by natural killer (NK) cells correlates with decreased infection risk in studies involving simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV), and human immunodeficiency virus (HIV) vaccine candidates. Currently, the heterogeneities of the functional subset of rhesus macaque natural killer (RMNK) cells are under-characterized.
Method: We engaged the RMNK cells with ADCC-mediating anti-HIV-1 monoclonal antibodies (ADCCAbs) or anti-CD16 antibodies and used CD107a expression as the surrogate marker for RMNK cells actively involved in ADCC. CD107a+ and CD107a– populations were analyzed individually using single-cell RNA sequencing.
Results: Subsets of CD107a+ RMNK cells produced more chemokines than the others, suggesting that these cells not only eliminate infected cells but also provide immunoregulatory signals and potentially curb HIV-1 replication. Crosslinking of Fc gamma receptor IIIa via anti-CD16 antibodies resulted in a significantly higher percentage of degranulating cells than via ADCCAbs. However, the magnitude of degranulation and chemokine production was reduced by 6- to 30-fold.
Conclusion: The quality and quantity of receptor engagement are important determinants of achieving an optimal level of the RMNK response.
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| format | Article |
| id | doaj-art-cedca063af7a41fb876a04bece882575 |
| institution | Kabale University |
| issn | 2469-2964 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Case Western Reserve University |
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| series | Pathogens and Immunity |
| spelling | doaj-art-cedca063af7a41fb876a04bece8825752025-01-24T20:28:11ZengCase Western Reserve UniversityPathogens and Immunity2469-29642025-01-0110110.20411/pai.v10i1.734Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated CytotoxicityJunsuke Nohara0Tyler Evangelous1Madison Berry2Whitney Beck3Sarah Mudrak4Shalini Jha5R. Keith Reeves6Kevin J. Wiehe7Justin Pollara8Georgia Tomaras9Todd Bradley10Guido Ferrari11https://orcid.org/0000-0001-7747-3349Department of Molecular Genetics and Microbiology, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine, Durham, NCHuman Vaccine Institute, Duke University School of Medicine, Durham, NCHuman Vaccine Institute, Duke University School of Medicine, Durham, NCHuman Vaccine Institute, Duke University School of Medicine, Durham, NCHuman Vaccine Institute, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine, Durham, NCDepartment of Surgery, Duke University School of Medicine, Durham, NCDepartment of Surgery, Duke University School of Medicine; Duke Research and Discovery at RTP, Duke University Health System; Center for Human Systems Immunology, Duke University; Department of Pathology, Duke University School of Medicine, Durham, NCHuman Vaccine Institute, Duke University School of Medicine, Durham, NCHuman Vaccine Institute, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine; Center for Human Systems Immunology, Duke University, Durham, NCDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine; Human Vaccine Institute, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine; Center for Human Systems Immunology, Duke University, Durham, NCGenomic Medicine Center, Children’s Mercy Research Institute, Children’s Mercy Kansas City; Departments of Pediatrics and Pathology and Laboratory Medicine, University of Kansas Medical Center; Department of Pediatrics, UMKC School of Medicine, Kansas City, MOHuman Vaccine Institute, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine; Center for Human Systems Immunology, Duke University, Durham, NC Background: Antibody-dependent cell-mediated cytotoxic (ADCC) response mediated by natural killer (NK) cells correlates with decreased infection risk in studies involving simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV), and human immunodeficiency virus (HIV) vaccine candidates. Currently, the heterogeneities of the functional subset of rhesus macaque natural killer (RMNK) cells are under-characterized. Method: We engaged the RMNK cells with ADCC-mediating anti-HIV-1 monoclonal antibodies (ADCCAbs) or anti-CD16 antibodies and used CD107a expression as the surrogate marker for RMNK cells actively involved in ADCC. CD107a+ and CD107a– populations were analyzed individually using single-cell RNA sequencing. Results: Subsets of CD107a+ RMNK cells produced more chemokines than the others, suggesting that these cells not only eliminate infected cells but also provide immunoregulatory signals and potentially curb HIV-1 replication. Crosslinking of Fc gamma receptor IIIa via anti-CD16 antibodies resulted in a significantly higher percentage of degranulating cells than via ADCCAbs. However, the magnitude of degranulation and chemokine production was reduced by 6- to 30-fold. Conclusion: The quality and quantity of receptor engagement are important determinants of achieving an optimal level of the RMNK response. https://www.paijournal.com/index.php/paijournal/article/view/734Rhesus MacaqueNK cellsAntibody-Dependent Cell CytotoxicitySingle-Cell Gene Expression AnalysisChemokine |
| spellingShingle | Junsuke Nohara Tyler Evangelous Madison Berry Whitney Beck Sarah Mudrak Shalini Jha R. Keith Reeves Kevin J. Wiehe Justin Pollara Georgia Tomaras Todd Bradley Guido Ferrari Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity Pathogens and Immunity Rhesus Macaque NK cells Antibody-Dependent Cell Cytotoxicity Single-Cell Gene Expression Analysis Chemokine |
| title | Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity |
| title_full | Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity |
| title_fullStr | Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity |
| title_full_unstemmed | Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity |
| title_short | Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity |
| title_sort | increased chemokine production is a hallmark of rhesus macaque natural killer cells mediating robust anti hiv envelope specific antibody dependent cell mediated cytotoxicity |
| topic | Rhesus Macaque NK cells Antibody-Dependent Cell Cytotoxicity Single-Cell Gene Expression Analysis Chemokine |
| url | https://www.paijournal.com/index.php/paijournal/article/view/734 |
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