A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals
The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation...
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| Veröffentlicht in: | AIDS research and human retroviruses 2013-10, Vol.29 (10), p.1353-1360 |
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| creator | Siewe, Basile Keshavarzian, Ali French, Audrey Demarais, Patricia Landay, Alan |
| description | The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART(+)). We evaluated activation markers implicated in B cell-mediated T cell trans infection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART(+) and HIV(-) subjects. However, B cells of HIVART(+) subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p |
| doi_str_mv | 10.1089/AID.2013.0115 |
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Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART(+)). We evaluated activation markers implicated in B cell-mediated T cell trans infection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART(+) and HIV(-) subjects. However, B cells of HIVART(+) subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p<0.0001), a marker of TLR signaling. In vitro, B cells of HIVART(+) individuals were less responsive to TLR stimulation compared to B cells of HIV(-) subjects. The activated phenotype of in vitro TLR-stimulated B cells of HIV(-) subjects was similar to ex vivo B cells from HIVART(+) individuals. TLR2 stimulation was a potent mediator of B cell activation, whereas B cells were least responsive to TLR4 stimulation. Compared to HIV(-) subjects, the serum level of lipoteichoic acid (TLR2 ligand) in HIVART(+) subjects was significantly higher (p=0.0207), correlating positively with viral load (p=0.0127, r=0.6453). Our data suggest that during HIV infection TLR-activated B cells may exert a pathogenic role and B cells from HIVART(+) subjects respond to in vitro TLR stimulation, yet exhibit a TLR tolerant phenotype suggesting prior in vivo TLR stimulation.</description><identifier>ISSN: 0889-2229</identifier><identifier>EISSN: 1931-8405</identifier><identifier>DOI: 10.1089/AID.2013.0115</identifier><identifier>PMID: 23763346</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Adult ; Aged ; AIDS/HIV ; Anti-Retroviral Agents - therapeutic use ; B-Lymphocytes - immunology ; Female ; Gene Expression Profiling ; HIV Infections - drug therapy ; HIV Infections - immunology ; Human immunodeficiency virus ; Humans ; Immunophenotyping ; Lymphocyte Activation ; Male ; Middle Aged ; Pathogenesis ; Retrovirus ; Signal Transduction ; Toll-Like Receptors - metabolism</subject><ispartof>AIDS research and human retroviruses, 2013-10, Vol.29 (10), p.1353-1360</ispartof><rights>Copyright 2013, Mary Ann Liebert, Inc. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-5475ad345d2fc23a4ff97e7fa6ceb8580622c52646ee5bbcec3dc3843e1e40cf3</citedby><cites>FETCH-LOGICAL-c464t-5475ad345d2fc23a4ff97e7fa6ceb8580622c52646ee5bbcec3dc3843e1e40cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3029,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23763346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siewe, Basile</creatorcontrib><creatorcontrib>Keshavarzian, Ali</creatorcontrib><creatorcontrib>French, Audrey</creatorcontrib><creatorcontrib>Demarais, Patricia</creatorcontrib><creatorcontrib>Landay, Alan</creatorcontrib><title>A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals</title><title>AIDS research and human retroviruses</title><addtitle>AIDS Res Hum Retroviruses</addtitle><description>The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART(+)). We evaluated activation markers implicated in B cell-mediated T cell trans infection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART(+) and HIV(-) subjects. However, B cells of HIVART(+) subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p<0.0001), a marker of TLR signaling. In vitro, B cells of HIVART(+) individuals were less responsive to TLR stimulation compared to B cells of HIV(-) subjects. The activated phenotype of in vitro TLR-stimulated B cells of HIV(-) subjects was similar to ex vivo B cells from HIVART(+) individuals. TLR2 stimulation was a potent mediator of B cell activation, whereas B cells were least responsive to TLR4 stimulation. Compared to HIV(-) subjects, the serum level of lipoteichoic acid (TLR2 ligand) in HIVART(+) subjects was significantly higher (p=0.0207), correlating positively with viral load (p=0.0127, r=0.6453). Our data suggest that during HIV infection TLR-activated B cells may exert a pathogenic role and B cells from HIVART(+) subjects respond to in vitro TLR stimulation, yet exhibit a TLR tolerant phenotype suggesting prior in vivo TLR stimulation.</description><subject>Adult</subject><subject>Aged</subject><subject>AIDS/HIV</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>B-Lymphocytes - immunology</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Lymphocyte Activation</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pathogenesis</subject><subject>Retrovirus</subject><subject>Signal Transduction</subject><subject>Toll-Like Receptors - metabolism</subject><issn>0889-2229</issn><issn>1931-8405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT1rHDEYhEVwiM92yrRBpZu96HulxnDx58FBINhpUgid9O5FZm_lSNqD_PvsYsckVaop5mGYYRD6QMmSEm0-rdZXS0YoXxJK5Ru0oIbTRgsij9CCaG0axpg5RielPBJCDGPyHTpmvFWcC7VA31c4px5wlzK-33zFJe4G18dhh8OYZ_mMPfQ9dr7Gg6sxDTgO2A01Zqg5HWJ2fVMzuAoB362_TW6IhxhG15cz9LabBN6_6Cl6uLm-v7xrNl9u15erTeOFErWRopUucCED6zzjTnSdaaHtnPKw1VITxZiXTAkFILdbD54Hz7XgQEEQ3_FTdPGc-zRu9xA8DHVqZZ9y3Lv8yyYX7b_OEH_YXTpY3mrZGjMFnL8E5PRzhFLtPpZ5thsgjcVSRTWVjEj-f1RwLZURgk1o84z6nErJ0L02osTO31kXg52_s_N3E__x7xmv9J-z-G8z5pYM</recordid><startdate>201310</startdate><enddate>201310</enddate><creator>Siewe, Basile</creator><creator>Keshavarzian, Ali</creator><creator>French, Audrey</creator><creator>Demarais, Patricia</creator><creator>Landay, Alan</creator><general>Mary Ann Liebert, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>201310</creationdate><title>A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals</title><author>Siewe, Basile ; Keshavarzian, Ali ; French, Audrey ; Demarais, Patricia ; Landay, Alan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-5475ad345d2fc23a4ff97e7fa6ceb8580622c52646ee5bbcec3dc3843e1e40cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>AIDS/HIV</topic><topic>Anti-Retroviral Agents - therapeutic use</topic><topic>B-Lymphocytes - immunology</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Lymphocyte Activation</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pathogenesis</topic><topic>Retrovirus</topic><topic>Signal Transduction</topic><topic>Toll-Like Receptors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siewe, Basile</creatorcontrib><creatorcontrib>Keshavarzian, Ali</creatorcontrib><creatorcontrib>French, Audrey</creatorcontrib><creatorcontrib>Demarais, Patricia</creatorcontrib><creatorcontrib>Landay, Alan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>AIDS research and human retroviruses</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siewe, Basile</au><au>Keshavarzian, Ali</au><au>French, Audrey</au><au>Demarais, Patricia</au><au>Landay, Alan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals</atitle><jtitle>AIDS research and human retroviruses</jtitle><addtitle>AIDS Res Hum Retroviruses</addtitle><date>2013-10</date><risdate>2013</risdate><volume>29</volume><issue>10</issue><spage>1353</spage><epage>1360</epage><pages>1353-1360</pages><issn>0889-2229</issn><eissn>1931-8405</eissn><abstract>The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART(+)). We evaluated activation markers implicated in B cell-mediated T cell trans infection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART(+) and HIV(-) subjects. However, B cells of HIVART(+) subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p<0.0001), a marker of TLR signaling. In vitro, B cells of HIVART(+) individuals were less responsive to TLR stimulation compared to B cells of HIV(-) subjects. The activated phenotype of in vitro TLR-stimulated B cells of HIV(-) subjects was similar to ex vivo B cells from HIVART(+) individuals. TLR2 stimulation was a potent mediator of B cell activation, whereas B cells were least responsive to TLR4 stimulation. Compared to HIV(-) subjects, the serum level of lipoteichoic acid (TLR2 ligand) in HIVART(+) subjects was significantly higher (p=0.0207), correlating positively with viral load (p=0.0127, r=0.6453). Our data suggest that during HIV infection TLR-activated B cells may exert a pathogenic role and B cells from HIVART(+) subjects respond to in vitro TLR stimulation, yet exhibit a TLR tolerant phenotype suggesting prior in vivo TLR stimulation.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>23763346</pmid><doi>10.1089/AID.2013.0115</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Mary Ann Liebert Online Subscription; MEDLINE; Alma/SFX Local Collection |
| subjects | Adult Aged AIDS/HIV Anti-Retroviral Agents - therapeutic use B-Lymphocytes - immunology Female Gene Expression Profiling HIV Infections - drug therapy HIV Infections - immunology Human immunodeficiency virus Humans Immunophenotyping Lymphocyte Activation Male Middle Aged Pathogenesis Retrovirus Signal Transduction Toll-Like Receptors - metabolism |
| title | A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals |
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