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

2020 07 15

Journal Article

Sharma, V.; Bryant, C.; Montero, M.; Creegan, M.; Slike, B.; Krebs, S.J.; Ratto-Kim, S.; Valcour, V.; Sithinamsuwan, P.; Chalermchai, T.; Eller, M.A.; Bolton, D.L.








Adult; Antiviral Agents; Case-Control Studies; CD4-Positive T-Lymphocytes; Cognitive Dysfunction; Female; Gene Expression; HIV Infections; HIV-1; Humans; Inflammation; Male; Middle Aged; Monocytes; neurocognitive disorders; Thailand; VID

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.

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