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ResearchIn-Press PreviewAIDS/HIVImmunology Open Access | 10.1172/jci.insight.202628

Granulocytic Myeloid-Derived Suppressor Cells Sustain HIV Reservoirs by Inhibiting Viral Reactivation via Arginase-1–Mediated Mechanisms

Ana Gallego-Cortés,1 Judith Grau-Expósito,1 Irene Mota-Gómez,1 Aleix Benitez-Martinez,1 Josep Castellvi,2 Jordi Navarro,1 Adrian Curran,1 Joaquin Burgos,1 Paula Suanzes,1 Vicenç Falcó,1 Meritxell Genescà,1 and Maria J. Buzon1

1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

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1Infectious Diseases Department, Universitat Autònoma de Barcelona, Barcelona, Spain

2Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

Find articles by Buzon, M. in: PubMed | Google Scholar |

Published July 21, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.202628.
Copyright © 2026, Gallego-Cortés et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 21, 2026 - Version history
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Abstract

Myeloid-Derived Suppressor Cells (MDSCs) represent a heterogeneous population of immature myeloid cells with potent immunosuppressive capabilities that contribute to viral persistence in chronic infections. However, their direct impact on the latent HIV reservoir remains poorly understood. Here, we report that people with HIV (PWH) exhibit elevated levels of MDSCs with notable immunosuppressive activity. Both granulocytic (G-MDSCs) and monocytic (M-MDSCs) subsets expressing arginase 1 (ARG1) or indoleamine 2,3-dioxygenase (IDO) are increased during treated infection, with low-level viral transcription preferentially associated with the expansion of highly suppressive G-MDSCs. Functional assays revealed that G-MDSCs robustly inhibit HIV reactivation from latent reservoirs. Mechanistically, G-MDSCs mediate this inhibition through a contact-independent mechanism, primarily involving ARG1 activity. Our findings demonstrate the capacity of G-MDSCs to sustain HIV reservoirs, suggesting that targeting these cells could potentiate therapeutic strategies aimed at eliminating HIV reservoirs through viral reactivation.

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