Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption
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 und...
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| Veröffentlicht in: | The Journal of clinical investigation 2020-06, Vol.130 (6), p.2845-2858 |
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| container_title | The Journal of clinical investigation |
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| creator | Mitchell, Julie L Takata, Hiroshi Muir, Roshell Colby, Donn J Kroon, Eugène Crowell, Trevor A Sacdalan, Carlo Pinyakorn, Suteeraporn Puttamaswin, Suwanna Benjapornpong, Khunthalee Trichavaroj, Rapee Tressler, Randall L Fox, Lawrence Polonis, Victoria R Bolton, Diane L Maldarelli, Frank Lewin, Sharon R Haddad, Elias K Phanuphak, Praphan Robb, Merlin L Michael, Nelson L de Souza, Mark Phanuphak, Nittaya Ananworanich, Jintanat Trautmann, Lydie |
| description | 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. |
| doi_str_mv | 10.1172/JCI130597 |
| format | Article |
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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.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI130597</identifier><identifier>PMID: 32017709</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Adult ; Antiretroviral drugs ; Antiretroviral therapy ; Biomedical research ; Blood ; Cytokines ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - pathology ; Drug therapy ; Female ; Health aspects ; Highly active antiretroviral therapy ; HIV ; HIV Infections - immunology ; HIV Infections - pathology ; HIV Infections - therapy ; HIV tests ; HIV-1 - physiology ; Human immunodeficiency virus ; Humans ; Infection ; Infections ; Interferon regulatory factor 7 ; Interferon Regulatory Factor-7 - immunology ; Interferon-alpha - immunology ; Male ; Maraviroc ; NF-kappa B - immunology ; NF-κB protein ; Phosphorylation ; Plasma ; Replication ; Ribonucleic acid ; RNA ; Scientific equipment industry ; Studies ; Viral infections ; Viremia ; Viremia - immunology ; Viremia - pathology ; Viremia - therapy ; Virus replication ; Virus Replication - immunology ; Vorinostat ; α-Interferon</subject><ispartof>The Journal of clinical investigation, 2020-06, Vol.130 (6), p.2845-2858</ispartof><rights>COPYRIGHT 2020 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Jun 2020</rights><rights>2020 American Society for Clinical Investigation 2020 American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c647t-3f97117092ae2f475cc2fa76cfc1b6d63168b60ff5afe2df8a0f9258efdfbd853</citedby><cites>FETCH-LOGICAL-c647t-3f97117092ae2f475cc2fa76cfc1b6d63168b60ff5afe2df8a0f9258efdfbd853</cites><orcidid>0000-0003-1369-3224 ; 0000-0003-2226-7825 ; 0000-0001-5947-265X ; 0000-0003-1457-6919 ; 0000-0003-3931-5926 ; 0000-0002-3062-5250 ; 0000-0003-3949-9649 ; 0000-0001-5882-5548 ; 0000-0003-1897-499X ; 0000-0002-5839-4837 ; 0000-0003-3880-4381 ; 0000-0001-6924-4300 ; 0000-0002-0036-3165 ; 0000-0002-3012-0009</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260031/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260031/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32017709$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mitchell, Julie L</creatorcontrib><creatorcontrib>Takata, Hiroshi</creatorcontrib><creatorcontrib>Muir, Roshell</creatorcontrib><creatorcontrib>Colby, Donn J</creatorcontrib><creatorcontrib>Kroon, Eugène</creatorcontrib><creatorcontrib>Crowell, Trevor A</creatorcontrib><creatorcontrib>Sacdalan, Carlo</creatorcontrib><creatorcontrib>Pinyakorn, Suteeraporn</creatorcontrib><creatorcontrib>Puttamaswin, Suwanna</creatorcontrib><creatorcontrib>Benjapornpong, Khunthalee</creatorcontrib><creatorcontrib>Trichavaroj, Rapee</creatorcontrib><creatorcontrib>Tressler, Randall L</creatorcontrib><creatorcontrib>Fox, Lawrence</creatorcontrib><creatorcontrib>Polonis, Victoria R</creatorcontrib><creatorcontrib>Bolton, Diane L</creatorcontrib><creatorcontrib>Maldarelli, Frank</creatorcontrib><creatorcontrib>Lewin, Sharon R</creatorcontrib><creatorcontrib>Haddad, Elias K</creatorcontrib><creatorcontrib>Phanuphak, Praphan</creatorcontrib><creatorcontrib>Robb, Merlin L</creatorcontrib><creatorcontrib>Michael, Nelson L</creatorcontrib><creatorcontrib>de Souza, Mark</creatorcontrib><creatorcontrib>Phanuphak, Nittaya</creatorcontrib><creatorcontrib>Ananworanich, Jintanat</creatorcontrib><creatorcontrib>Trautmann, Lydie</creatorcontrib><creatorcontrib>RV397, RV411, and RV254 Study Groups</creatorcontrib><title>Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>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.</description><subject>Adult</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Biomedical research</subject><subject>Blood</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - pathology</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Health aspects</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - pathology</subject><subject>HIV Infections - therapy</subject><subject>HIV tests</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infection</subject><subject>Infections</subject><subject>Interferon regulatory factor 7</subject><subject>Interferon Regulatory Factor-7 - immunology</subject><subject>Interferon-alpha - immunology</subject><subject>Male</subject><subject>Maraviroc</subject><subject>NF-kappa B - immunology</subject><subject>NF-κB protein</subject><subject>Phosphorylation</subject><subject>Plasma</subject><subject>Replication</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Scientific equipment industry</subject><subject>Studies</subject><subject>Viral infections</subject><subject>Viremia</subject><subject>Viremia - immunology</subject><subject>Viremia - pathology</subject><subject>Viremia - therapy</subject><subject>Virus replication</subject><subject>Virus Replication - 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dendritic cells sense HIV replication before detectable viremia following treatment interruption</title><author>Mitchell, Julie L ; Takata, Hiroshi ; Muir, Roshell ; Colby, Donn J ; Kroon, Eugène ; Crowell, Trevor A ; Sacdalan, Carlo ; Pinyakorn, Suteeraporn ; Puttamaswin, Suwanna ; Benjapornpong, Khunthalee ; Trichavaroj, Rapee ; Tressler, Randall L ; Fox, Lawrence ; Polonis, Victoria R ; Bolton, Diane L ; Maldarelli, Frank ; Lewin, Sharon R ; Haddad, Elias K ; Phanuphak, Praphan ; Robb, Merlin L ; Michael, Nelson L ; de Souza, Mark ; Phanuphak, Nittaya ; Ananworanich, Jintanat ; Trautmann, Lydie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c647t-3f97117092ae2f475cc2fa76cfc1b6d63168b60ff5afe2df8a0f9258efdfbd853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral therapy</topic><topic>Biomedical 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Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mitchell, Julie L</au><au>Takata, Hiroshi</au><au>Muir, Roshell</au><au>Colby, Donn J</au><au>Kroon, Eugène</au><au>Crowell, Trevor A</au><au>Sacdalan, Carlo</au><au>Pinyakorn, Suteeraporn</au><au>Puttamaswin, Suwanna</au><au>Benjapornpong, Khunthalee</au><au>Trichavaroj, Rapee</au><au>Tressler, Randall L</au><au>Fox, Lawrence</au><au>Polonis, Victoria R</au><au>Bolton, Diane L</au><au>Maldarelli, Frank</au><au>Lewin, Sharon R</au><au>Haddad, Elias K</au><au>Phanuphak, Praphan</au><au>Robb, Merlin L</au><au>Michael, Nelson L</au><au>de Souza, Mark</au><au>Phanuphak, Nittaya</au><au>Ananworanich, Jintanat</au><au>Trautmann, Lydie</au><aucorp>RV397, RV411, and RV254 Study Groups</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>130</volume><issue>6</issue><spage>2845</spage><epage>2858</epage><pages>2845-2858</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><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.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>32017709</pmid><doi>10.1172/JCI130597</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-1369-3224</orcidid><orcidid>https://orcid.org/0000-0003-2226-7825</orcidid><orcidid>https://orcid.org/0000-0001-5947-265X</orcidid><orcidid>https://orcid.org/0000-0003-1457-6919</orcidid><orcidid>https://orcid.org/0000-0003-3931-5926</orcidid><orcidid>https://orcid.org/0000-0002-3062-5250</orcidid><orcidid>https://orcid.org/0000-0003-3949-9649</orcidid><orcidid>https://orcid.org/0000-0001-5882-5548</orcidid><orcidid>https://orcid.org/0000-0003-1897-499X</orcidid><orcidid>https://orcid.org/0000-0002-5839-4837</orcidid><orcidid>https://orcid.org/0000-0003-3880-4381</orcidid><orcidid>https://orcid.org/0000-0001-6924-4300</orcidid><orcidid>https://orcid.org/0000-0002-0036-3165</orcidid><orcidid>https://orcid.org/0000-0002-3012-0009</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9738 |
| ispartof | The Journal of clinical investigation, 2020-06, Vol.130 (6), p.2845-2858 |
| issn | 0021-9738 1558-8238 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7260031 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adult Antiretroviral drugs Antiretroviral therapy Biomedical research Blood Cytokines Dendritic cells Dendritic Cells - immunology Dendritic Cells - pathology Drug therapy Female Health aspects Highly active antiretroviral therapy HIV HIV Infections - immunology HIV Infections - pathology HIV Infections - therapy HIV tests HIV-1 - physiology Human immunodeficiency virus Humans Infection Infections Interferon regulatory factor 7 Interferon Regulatory Factor-7 - immunology Interferon-alpha - immunology Male Maraviroc NF-kappa B - immunology NF-κB protein Phosphorylation Plasma Replication Ribonucleic acid RNA Scientific equipment industry Studies Viral infections Viremia Viremia - immunology Viremia - pathology Viremia - therapy Virus replication Virus Replication - immunology Vorinostat α-Interferon |
| title | Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T09%3A32%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Plasmacytoid%20dendritic%20cells%20sense%20HIV%20replication%20before%20detectable%20viremia%20following%20treatment%20interruption&rft.jtitle=The%20Journal%20of%20clinical%20investigation&rft.au=Mitchell,%20Julie%20L&rft.aucorp=RV397,%20RV411,%20and%20RV254%20Study%20Groups&rft.date=2020-06-01&rft.volume=130&rft.issue=6&rft.spage=2845&rft.epage=2858&rft.pages=2845-2858&rft.issn=0021-9738&rft.eissn=1558-8238&rft_id=info:doi/10.1172/JCI130597&rft_dat=%3Cgale_pubme%3EA627278054%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2414425187&rft_id=info:pmid/32017709&rft_galeid=A627278054&rfr_iscdi=true |