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Viruses 2018, 10(4), 154; https://doi.org/10.3390/v10040154

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
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 7 March 2018 / Revised: 24 March 2018 / Accepted: 26 March 2018 / Published: 28 March 2018
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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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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