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Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption
Julie L. Mitchell, … , Lydie Trautmann, on behalf of the RV397, RV411, and RV254 Study Groups
Julie L. Mitchell, … , Lydie Trautmann, on behalf of the RV397, RV411, and RV254 Study Groups
Published February 4, 2020
Citation Information: J Clin Invest. 2020;130(6):2845-2858. https://doi.org/10.1172/JCI130597.
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Research Article AIDS/HIV Immunology

Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption

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Abstract

Plasmacytoid dendritic cells (pDCs) are robust producers of IFNα and one of the first immune cells to respond to SIV infection. To elucidate responses to early HIV-1 replication, we studied blood pDCs in 29 HIV-infected participants who initiated antiretroviral therapy during acute infection and underwent analytic treatment interruption (ATI). We observed an increased frequency of partially activated pDCs in the blood before detection of HIV RNA. Concurrent with peak pDC frequency, we detected a transient decline in the ability of pDCs to produce IFNα in vitro, which correlated with decreased phosphorylation of IFN regulatory factory 7 (IRF7) and NF-κB. The levels of phosphorylated IRF7 and NF-κB inversely correlated with plasma IFNα2 levels, implying that pDCs were refractory to in vitro stimulation after IFNα production in vivo. After ATI, decreased expression of IFN genes in pDCs inversely correlated with the time to viral detection, suggesting that pDC IFN loss is part of an effective early immune response. These data from a limited cohort provide a critical first step in understanding the earliest immune response to HIV-1 and suggest that changes in blood pDC frequency and function can be used as an indicator of viral replication before detectable plasma viremia.

Authors

Julie L. Mitchell, Hiroshi Takata, Roshell Muir, Donn J. Colby, Eugène Kroon, Trevor A. Crowell, Carlo Sacdalan, Suteeraporn Pinyakorn, Suwanna Puttamaswin, Khunthalee Benjapornpong, Rapee Trichavaroj, Randall L. Tressler, Lawrence Fox, Victoria R. Polonis, Diane L. Bolton, Frank Maldarelli, Sharon R. Lewin, Elias K. Haddad, Praphan Phanuphak, Merlin L. Robb, Nelson L. Michael, Mark de Souza, Nittaya Phanuphak, Jintanat Ananworanich, Lydie Trautmann, on behalf of the RV397, RV411, and RV254 Study Groups

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Figure 1

Frequency of pDCs in the blood increases before detectable viremia.

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Frequency of pDCs in the blood increases before detectable viremia.
(A) ...
(A) pDCs were identified as CD45+HLA-DR+CD303+ cells that were negative for CD14, CD11c, and CD1c and the lineage markers CD3, CD14, CD19, and CD56 (Lin–). (B) The frequency of pDCs in the blood was measured by flow cytometry as a percentage of lineage-negative cells. Representative graphs show the pDC frequency (blue) relative to the VL after ATI (black). (C) The pDC frequency at the time of ATI was compared with the frequency at the last aviremic time point to show increased pDC frequency before viral RNA was detected in the blood. ***P < 0.001, by Wilcoxon test. n = 25 (10 of whom received VRC01). (D) The frequency of pDCs in the blood before ATI is shown for the 5 participants in the placebo arm of RV409. Changes in pDC frequency were compared when measurements were taken at a 2- or 4-week time interval.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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