Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity

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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Main Authors: 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
Format: Article
Language:English
Published: Case Western Reserve University 2025-01-01
Series:Pathogens and Immunity
Subjects:
Rhesus Macaque
NK cells
Antibody-Dependent Cell Cytotoxicity
Single-Cell Gene Expression Analysis
Chemokine
Online Access:https://www.paijournal.com/index.php/paijournal/article/view/734
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Summary: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.
ISSN:2469-2964

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