Macrophage polarization drives viral reservoirs in HIV-1 infection
5 affiliations
- 1Laboratory of Immunology, Infectious and Allergic Diseases, Institute of Applied Biomedical Sciences, Faculty of Sciences and Technology, University of Abomey-Calavi
- 2Departments of Virology Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana
- 3Departments of Immunology Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana
- 4Medical and Scientific Research Centre, University of Ghana Medical Centre
- 5Departments of Medicine and Molecular Microbiology, Washington University in St. Louis
Abstract
Macrophages are cells of the myeloid lineage that play a very important role in innate immunity and tissue homeostasis. They have the capacity to respond to aggression from pathogenic agents and are the target of HIV-1 infection via their CD4 receptor and the CCR5 and CXCR4 co-receptors. In People With HIV (PWH), macrophages constitute a virological reservoir, making treatment with Antiretroviral Therapy (ART) difficult as they are resistant to the cytopathic effect induced by the virus, resist apoptosis and are in parts of the body with limited access, such as the brain. During HIV infection, macrophages are activated and polarized with the aim of eliminating the virus. Based on their polarization, they are classified into three main groups during HIV infection: M1 and M4 macrophages, which are classically activated, and M2 macrophages, which are activated alternatively. M2 macrophages are subdivided into several subtypes: M2a, M2b, M2c and M2d. M1 and M4 macrophages are pro-inflammatory and are stimulated by pro-inflammatory cytokines such as IL-2, IL-1r and TNF-α. M2 macrophages are anti-inflammatory and are stimulated by anti-inflammatory cytokines such as IL-4, IL-10 and IL-13. Macrophages constitute a very significant and long-lasting viral reservoir due to their intrinsic longevity. Furthermore, the accumulation of virions within Virus-Containing Compartments (VCCs) maintains the latent virus, thereby demonstrating their role as a critical, stable and long-lasting reservoir. However, the reservoir establishment and the persistence of the virus in polarized macrophages have not been fully explored. In this review, we examined macrophage polarization dynamics during HIV infection and explained how polarized macrophages contribute to the establishment of viral reservoirs. We also discuss how the acquisition of specific phenotypes may be a key factor in HIV reservoir formation. Thus, providing important information to guide reactivation of HIV from macrophages, a critical step in the Shock-and-Kill HIV cure strategy.
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BibTeX
@article{glokpon2026macrophage,
title = {{Macrophage polarization drives viral reservoirs in HIV-1 infection}},
author = {Aldo Emmanuel Calicio Glokpon and Sedaminou Judith Gbenoudon and Christopher Zaab-Yen Abana and Prince Adom Nartey and Jonathan Klutse and Helena Lamptey and Evelyn Yayra Bonney and George Boateng Kyei},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1941085},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1941085/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Macrophage polarization drives viral reservoirs in HIV-1 infection
AU - Aldo Emmanuel Calicio Glokpon
AU - Sedaminou Judith Gbenoudon
AU - Christopher Zaab-Yen Abana
AU - Prince Adom Nartey
AU - Jonathan Klutse
AU - Helena Lamptey
AU - Evelyn Yayra Bonney
AU - George Boateng Kyei
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1941085
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1941085/full
AB - Macrophages are cells of the myeloid lineage that play a very important role in innate immunity and tissue homeostasis. They have the capacity to respond to aggression from pathogenic agents and are the target of HIV-1 infection via their CD4 receptor and the CCR5 and CXCR4 co-receptors. In People With HIV (PWH), macrophages constitute a virological reservoir, making treatment with Antiretroviral Therapy (ART) difficult as they are resistant to the cytopathic effect induced by the virus, resist apoptosis and are in parts of the body with limited access, such as the brain. During HIV infection, macrophages are activated and polarized with the aim of eliminating the virus. Based on their polarization, they are classified into three main groups during HIV infection: M1 and M4 macrophages, which are classically activated, and M2 macrophages, which are activated alternatively. M2 macrophages are subdivided into several subtypes: M2a, M2b, M2c and M2d. M1 and M4 macrophages are pro-inflammatory and are stimulated by pro-inflammatory cytokines such as IL-2, IL-1r and TNF-α. M2 macrophages are anti-inflammatory and are stimulated by anti-inflammatory cytokines such as IL-4, IL-10 and IL-13. Macrophages constitute a very significant and long-lasting viral reservoir due to their intrinsic longevity. Furthermore, the accumulation of virions within Virus-Containing Compartments (VCCs) maintains the latent virus, thereby demonstrating their role as a critical, stable and long-lasting reservoir. However, the reservoir establishment and the persistence of the virus in polarized macrophages have not been fully explored. In this review, we examined macrophage polarization dynamics during HIV infection and explained how polarized macrophages contribute to the establishment of viral reservoirs. We also discuss how the acquisition of specific phenotypes may be a key factor in HIV reservoir formation. Thus, providing important information to guide reactivation of HIV from macrophages, a critical step in the Shock-and-Kill HIV cure strategy.
SN - 1664-3224
ER -