Details

Autor(en) / Beteiligte

• Sharma, Vishakha
• Bryant, Christopher
• Montero, Maria
• Creegan, Matthew
• Slike, Bonnie
• Krebs, Shelly J
• Ratto-Kim, Silvia
• Valcour, Victor
• Sithinamsuwan, Pasiri
• Chalermchai, Thep
• Eller, Michael A
• Bolton, Diane L

Titel

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

Ist Teil von

• AIDS (London), 2020-07, Vol.34 (9), p.1289-1301

Ort / Verlag

England: Copyright Wolters Kluwer Health, Inc

Erscheinungsjahr

2020

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.