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Monocyte and CD4+ T-cell antiviral and innate responses associated with HIV-1 inflammation and cognitive impairment.
- Source :
-
AIDS (London, England) [AIDS] 2020 Jul 15; Vol. 34 (9), pp. 1289-1301. - Publication Year :
- 2020
-
Abstract
- Objective: Mechanisms underlying immune activation and HIV-associated neurocognitive disorders (HAND) in untreated chronic infection remain unclear. The objective of this study was to identify phenotypic and transcriptional changes in blood monocytes and CD4 T cells in HIV-1-infected and uninfected individuals and elucidate processes associated with neurocognitive impairment.<br />Design: A group of chronically HIV-1-infected Thai individuals (n = 19) were selected for comparison with healthy donor controls (n = 10). Infected participants were further classified as cognitively normal (n = 10) or with HAND (n = 9). Peripheral monocytes and CD4 T cells were phenotyped by flow cytometry and simultaneously isolated for multiplex qPCR-targeted gene expression profiling directly ex vivo. The frequency of HIV-1 RNA-positive cells was estimated by limiting dilution cell sorting.<br />Results: Expression of genes and proteins involved in cellular activation and proinflammatory immune responses was increased in monocytes and CD4 T cells from HIV-1-infected relative to uninfected individuals. Gene expression profiles of both CD4 T cells and monocytes correlated with soluble markers of inflammation in the periphery (P < 0.05). By contrast, only modest differences in gene programs were observed between cognitively normal and HAND cases. These included increased monocyte surface CD169 protein expression relative to cognitively normal (P = 0.10), decreased surface CD163 expression relative to uninfected (P = 0.02) and cognitively normal (P = 0.06), and downregulation of EMR2 (P = 0.04) and STAT1 (P = 0.02) relative to cognitively normal.<br />Conclusion: Our data support a model of highly activated monocytes and CD4 T cells associated with inflammation in chronic HIV-1 infection, but impaired monocyte anti-inflammatory responses in HAND compared with cognitively normal.
- Subjects :
- Adult
Antiviral Agents therapeutic use
CD4-Positive T-Lymphocytes pathology
Case-Control Studies
Cognitive Dysfunction diagnosis
Cognitive Dysfunction psychology
Female
Gene Expression
HIV Infections drug therapy
HIV-1 isolation & purification
Humans
Male
Middle Aged
Monocytes drug effects
Neurocognitive Disorders diagnosis
Thailand
CD4-Positive T-Lymphocytes drug effects
Cognitive Dysfunction etiology
HIV Infections complications
HIV Infections immunology
HIV-1 genetics
Inflammation immunology
Monocytes pathology
Neurocognitive Disorders etiology
Neurocognitive Disorders psychology
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5571
- Volume :
- 34
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- AIDS (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 32598115
- Full Text :
- https://doi.org/10.1097/QAD.0000000000002537