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Antigen Presenting Cells Contribute to Persistent Immune Activation Despite Antiretroviral Therapy Initiation During Hyperacute HIV-1 Infection.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Sep 24; Vol. 12, pp. 738743. Date of Electronic Publication: 2021 Sep 24 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- Human immunodeficiency virus (HIV)-induced changes in immune cells during the acute phase of infection can cause irreversible immunological damage and predict the rate of disease progression. Antiretroviral therapy (ART) remains the most effective strategy for successful immune restoration in immunocompromised people living with HIV and the earlier ART is initiated after infection, the better the long-term clinical outcomes. Here we explored the effect of ART on peripheral antigen presenting cell (APC) phenotype and function in women with HIV-1 subtype C infection who initiated ART in the hyperacute phase (before peak viremia) or during chronic infection. Peripheral blood mononuclear cells obtained longitudinally from study participants were used for immunophenotyping and functional analysis of monocytes and dendritic cells (DCs) using multiparametric flow cytometry and matched plasma was used for measurement of inflammatory markers IL-6 and soluble CD14 (sCD14) by enzyme-linked immunosorbent assay. HIV infection was associated with expansion of monocyte and plasmacytoid DC (pDC) frequencies and perturbation of monocyte subsets compared to uninfected persons despite antiretroviral treatment during hyperacute infection. Expression of activation marker CD69 on monocytes and pDCs in early treated HIV was similar to uninfected individuals. However, despite early ART, HIV infection was associated with elevation of plasma IL-6 and sCD14 levels which correlated with monocyte activation. Furthermore, HIV infection with or without early ART was associated with downmodulation of the co-stimulatory molecule CD86. Notably, early ART was associated with preserved toll-like receptor (TLR)-induced IFN-α responses of pDCs. Overall, this data provides evidence of the beneficial impact of ART initiated in hyperacute infection in preservation of APC functional cytokine production activity; but also highlights persistent inflammation facilitated by monocyte activation even after prolonged viral suppression and suggests the need for therapeutic interventions that target residual immune activation.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Naidoo, Ndumnego, Ismail, Dong and Ndung’u.)
- Subjects :
- Adolescent
Antigens, CD metabolism
Antigens, Differentiation, T-Lymphocyte metabolism
B7-2 Antigen metabolism
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes virology
Cytokines metabolism
Dendritic Cells immunology
Dendritic Cells metabolism
Dendritic Cells virology
Female
HIV Infections immunology
HIV Infections virology
HIV-1 immunology
HIV-1 pathogenicity
Host-Pathogen Interactions
Humans
Lectins, C-Type metabolism
Lipopolysaccharide Receptors metabolism
Longitudinal Studies
Monocytes immunology
Monocytes metabolism
Monocytes virology
Phenotype
Pilot Projects
Time Factors
Treatment Outcome
Viral Load
Young Adult
Anti-Retroviral Agents therapeutic use
Dendritic Cells drug effects
HIV Infections drug therapy
HIV-1 drug effects
Monocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34630420
- Full Text :
- https://doi.org/10.3389/fimmu.2021.738743