TY - JOUR
T1 - Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption
AU - Mitchell, Julie L.
AU - Takata, Hiroshi
AU - Muir, Roshell
AU - Colby, Donn J.
AU - Kroon, Eugène
AU - Crowell, Trevor A.
AU - Sacdalan, Carlo
AU - Pinyakorn, Suteeraporn
AU - Puttamaswin, Suwanna
AU - Benjapornpong, Khunthalee
AU - Trichavaroj, Rapee
AU - Tressler, Randall L.
AU - Fox, Lawrence
AU - Polonis, Victoria R.
AU - Bolton, Diane L.
AU - Maldarelli, Frank
AU - Lewin, Sharon R.
AU - Haddad, Elias K.
AU - Phanuphak, Praphan
AU - Robb, Merlin L.
AU - Michael, Nelson L.
AU - De Souza, Mark
AU - Phanuphak, Nittaya
AU - Ananworanich, Jintanat
AU - Trautmann, Lydie
N1 - Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085905232&partnerID=8YFLogxK
U2 - 10.1172/JCI130597
DO - 10.1172/JCI130597
M3 - Article
C2 - 32017709
AN - SCOPUS:85085905232
SN - 0021-9738
VL - 130
SP - 2845
EP - 2858
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 6
ER -