Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption
Open Access
- 1 June 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (6), 2845-2858
- https://doi.org/10.1172/JCI130597
Abstract
Plasmacytoid dendritic cells (pDCs) are robust producers of IFN alpha 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 IFN alpha in vitro, which correlated with decreased phosphorylation of IFN regulatory factory 7 (IRF7) and NF-kappa B. The levels of phosphorylated IRF7 and NF-kappa B inversely correlated with plasma IFN alpha 2 levels, implying that pDCs were refractory to in vitro stimulation after IFN alpha 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.Funding Information
- National Institute of Allergy and Infectious Diseases (R01AI108433)
- U.S. Department of Defense (W81XWH-07-2-0067, W81XWH-11-2-0174)
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