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Monocyte and CD4(+)T-cell antiviral and innate responses associated with HIV-1 inflammation and cognitive impairment

机译:单核细胞和CD4(+)T细胞抗病毒和与HIV-1炎症和认知障碍相关的先天反应

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摘要

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 directlyex 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 ofEMR2(P = 0.04) andSTAT1(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.
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