1. Monocyte and CD4+ T-cell antiviral and innate responses associated with HIV-1 inflammation and cognitive impairment.
- Author
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Sharma V, Bryant C, Montero M, Creegan M, Slike B, Krebs SJ, Ratto-Kim S, Valcour V, Sithinamsuwan P, Chalermchai T, Eller MA, and Bolton DL
- 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
- 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., 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., 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., 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.
- Published
- 2020
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