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Open AccessArticle

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

1
Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic
2
Department of Genetics and Microbiology, Charles University, Faculty of Sciences, BIOCEV, 25242 Vestec, Czech Republic
3
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, IOCB & Gilead Research Center, 16610 Prague, Czech Republic
4
The Third Faculty of Medicine, Charles University and Hospital Na Bulovce, 18081 Prague, Czech Republic
5
The First Faculty of Medicine, Charles University and Hospital Na Bulovce, 18081 Prague, Czech Republic
6
Department of Immunology and Microbiology, Charles University, The First Faculty of Medicine, BIOCEV, 25242 Vestec, Czech Republic
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2018, 10(4), 154; https://doi.org/10.3390/v10040154
Received: 7 March 2018 / Revised: 24 March 2018 / Accepted: 26 March 2018 / Published: 28 March 2018
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. View Full-Text
Keywords: HIV-1; antiretroviral therapy (ART); innate and adaptive immune responses; plasmacytoid dendritic cells (pDCs); pDC dysfunction; T cell Ig and mucin-domain containing molecule 3 (TIM-3); BDCA-2; Toll-like receptors 7 and 9 (TLR7/9) HIV-1; antiretroviral therapy (ART); innate and adaptive immune responses; plasmacytoid dendritic cells (pDCs); pDC dysfunction; T cell Ig and mucin-domain containing molecule 3 (TIM-3); BDCA-2; Toll-like receptors 7 and 9 (TLR7/9)
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MDPI and ACS Style

Font-Haro, A.; Janovec, V.; Hofman, T.; Machala, L.; Jilich, D.; Melkova, Z.; Weber, J.; Trejbalova, K.; Hirsch, I. Expression of TIM-3 on Plasmacytoid Dendritic Cells as a Predictive Biomarker of Decline in HIV-1 RNA Level during ART. Viruses 2018, 10, 154.

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