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Expression of TIM-3 on Plasmacytoid Dendritic Cells as a Predictive Biomarker of Decline in HIV-1 RNA Level during ART

A. Font-Haro, V. Janovec, T. Hofman, L. Machala, D. Jilich, Z. Melkova, J. Weber, K. Trejbalova, I. Hirsch,

. 2018 ; 10 (4) : . [pub] 20180328

Language English Country Switzerland

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc18033211

Depletion and functional impairment of circulating plasmacytoid dendritic cells (pDCs) are characteristic attributes of HIV-1-infection. The mechanism of dysfunction of pDCs is unclear. Here, we studied the development of phenotype of pDCs in a cohort of HIV-1-infected individuals monitored before the initiation and during a 9-month follow up with antiretroviral therapy (ART). Using polychromatic flow cytometry, we detected significantly higher pDC-surface expression of the HIV-1 receptor CD4, regulatory receptor BDCA-2, Fcγ receptor CD32, pDC dysfunction marker TIM-3, and the marker of killer pDC, TRAIL, in treatment-naïve HIV-1-infected individuals before initiation of ART when compared to healthy donors. After 9 months of ART, all of these markers approached but did not reach the expression levels observed in healthy donors. We found that the rate of decline in HIV-1 RNA level over the first 3 months of ART negatively correlated with the expression of TIM-3 on pDCs. We conclude that immunogenic phenotype of pDCs is not significantly restored after sustained suppression of HIV-1 RNA level in ART-treated patients and that the level of the TIM-3 expressed on pDCs in treatment naïve patients could be a predictive marker of the rate of decline in the HIV-1 RNA level during ART.

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$a Font-Haro, Albert $u Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic. afont.haro@gmail.com. Department of Genetics and Microbiology, Charles University, Faculty of Sciences, BIOCEV, 25242 Vestec, Czech Republic. afont.haro@gmail.com. Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, IOCB & Gilead Research Center, 16610 Prague, Czech Republic. afont.haro@gmail.com.
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$a Depletion and functional impairment of circulating plasmacytoid dendritic cells (pDCs) are characteristic attributes of HIV-1-infection. The mechanism of dysfunction of pDCs is unclear. Here, we studied the development of phenotype of pDCs in a cohort of HIV-1-infected individuals monitored before the initiation and during a 9-month follow up with antiretroviral therapy (ART). Using polychromatic flow cytometry, we detected significantly higher pDC-surface expression of the HIV-1 receptor CD4, regulatory receptor BDCA-2, Fcγ receptor CD32, pDC dysfunction marker TIM-3, and the marker of killer pDC, TRAIL, in treatment-naïve HIV-1-infected individuals before initiation of ART when compared to healthy donors. After 9 months of ART, all of these markers approached but did not reach the expression levels observed in healthy donors. We found that the rate of decline in HIV-1 RNA level over the first 3 months of ART negatively correlated with the expression of TIM-3 on pDCs. We conclude that immunogenic phenotype of pDCs is not significantly restored after sustained suppression of HIV-1 RNA level in ART-treated patients and that the level of the TIM-3 expressed on pDCs in treatment naïve patients could be a predictive marker of the rate of decline in the HIV-1 RNA level during ART.
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$a Janovec, Vaclav $u Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic. vaclav.janovec@natur.cuni.cz. Department of Genetics and Microbiology, Charles University, Faculty of Sciences, BIOCEV, 25242 Vestec, Czech Republic. vaclav.janovec@natur.cuni.cz. Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, IOCB & Gilead Research Center, 16610 Prague, Czech Republic. vaclav.janovec@natur.cuni.cz.
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$a Hofman, Tomas $u Department of Genetics and Microbiology, Charles University, Faculty of Sciences, BIOCEV, 25242 Vestec, Czech Republic. tomas.hofman@volny.cz.
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$a Machala, Ladislav $u The Third Faculty of Medicine, Charles University and Hospital Na Bulovce, 18081 Prague, Czech Republic. ladimachala@centrum.cz.
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$a Jilich, David $u The First Faculty of Medicine, Charles University and Hospital Na Bulovce, 18081 Prague, Czech Republic. david.jilich@centrum.cz.
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$a Melkova, Zora $u Department of Immunology and Microbiology, Charles University, The First Faculty of Medicine, BIOCEV, 25242 Vestec, Czech Republic. zmelk@lf1.cuni.cz.
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$a Weber, Jan $u Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, IOCB & Gilead Research Center, 16610 Prague, Czech Republic. weber@uochb.cas.cz.
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$a Trejbalova, Katerina $u Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic. katerina.trejbalova@img.cas.cz.
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$a Hirsch, Ivan $u Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic. hirschi@natur.cuni.cz. Department of Genetics and Microbiology, Charles University, Faculty of Sciences, BIOCEV, 25242 Vestec, Czech Republic. hirschi@natur.cuni.cz. Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, IOCB & Gilead Research Center, 16610 Prague, Czech Republic. hirschi@natur.cuni.cz.
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