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

Publication Type
Journal Article
Year of Publication
2020
Authors
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; SEARCH007/SEARCH011 Study Groups
Secondary
AIDS
Volume
34
Pagination
1289-1301
Date Published
2020 07 15
Keywords
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
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.

URL
https://pubmed.ncbi.nlm.nih.gov/32598115/