{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T18:19:38Z","timestamp":1773685178702,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Monocyte-derived macrophages (MDM) can polarize into different subsets depending on the environment and the activation signal to which they are submitted. Differentiation into macrophages allows HIV-1 strains to infect cells of the monocytic lineage. In this study, we show that culture of monocytes with a combination of IL-12 and IL-18 led to macrophage differentiation that was resistant to HIV-1 infection. In contrast, M-CSF\u2013derived MDM were readily infected by HIV-1. When monocytes were differentiated in the presence of M-CSF and then further treated with IL-12\/IL-18, cells became resistant to infection. The restriction on HIV-1 replication was not dependent on virus entry or coreceptor expression, as vesicular stomatitis virus-pseudotyped HIV-1 replication was also blocked by IL-12\/IL-18. The HIV-1 restriction factor sterile \u03b1 motif and HD domain\u2013containing protein-1 (SAMHD1) was significantly overexpressed in IL-12\/IL-18 MDM compared with M-CSF MDM, and degradation of SAMHD1 by RNA interference or viral-like particles carrying the lentiviral protein Vpx restored HIV-1 infectivity of IL-12\/IL-18 MDM. SAMHD1 overexpression induced by IL-12\/IL-18 was not dependent on IFN-\u03b3. Thus, we conclude that IL-12 and IL-18 may contribute to the response against HIV-1 infection through the induction of restriction factors such as SAMHD1.<\/jats:p>","DOI":"10.4049\/jimmunol.1203226","type":"journal-article","created":{"date-parts":[[2013,3,23]],"date-time":"2013-03-23T04:36:43Z","timestamp":1364013403000},"page":"4736-4741","source":"Crossref","is-referenced-by-count":47,"title":["Restriction of HIV-1 Replication in Primary Macrophages by IL-12 and IL-18 through the Upregulation of SAMHD1"],"prefix":"10.1093","volume":"190","author":[{"given":"Eduardo","family":"Pauls","sequence":"first","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Esther","family":"Jimenez","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Alba","family":"Ruiz","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Marc","family":"Permanyer","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Ester","family":"Ballana","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Helena","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ciencia , 2780-156 Oeiras,","place":["Portugal"]}]},{"given":"Rute","family":"Nascimiento","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ciencia , 2780-156 Oeiras,","place":["Portugal"]}]},{"given":"R Michael","family":"Parkhouse","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ciencia , 2780-156 Oeiras,","place":["Portugal"]}]},{"given":"Ruth","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Eva","family":"Riveiro-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Miguel A","family":"Martinez","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Bonaventura","family":"Clotet","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Jos\u00e9 A","family":"Est\u00e9","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]}]},{"given":"Margarida","family":"Bofill","sequence":"additional","affiliation":[{"name":"IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona , 08916 Badalona,","place":["Spain"]},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats , 08010 Barcelona,","place":["Spain"]}]}],"member":"286","published-online":{"date-parts":[[2013,5,1]]},"reference":[{"key":"2025032406582237600_r1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1189\/jlb.1009673","article-title":"Macrophage polarization and HIV-1 infection","volume":"87","author":"Cassol","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"2025032406582237600_r2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/ni.1990","article-title":"IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses","volume":"12","author":"Krausgruber","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025032406582237600_r3","doi-asserted-by":"crossref","first-page":"5752","DOI":"10.4049\/jimmunol.1103426","article-title":"Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models","volume":"188","author":"Lacey","year":"2012","journal-title":"J. Immunol."},{"key":"2025032406582237600_r4","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nri2448","article-title":"Exploring the full spectrum of macrophage activation","volume":"8","author":"Mosser","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025032406582237600_r5","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1365-2249.2006.03145.x","article-title":"Treatment of monocytes with interleukin (IL)-12 plus IL-18 stimulates survival, differentiation and the production of CXC chemokine ligands (CXCL)8, CXCL9 and CXCL10","volume":"145","author":"Coma","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"2025032406582237600_r6","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1365-2567.2008.02905.x","article-title":"Secretion of interferon-\u03b3 by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18","volume":"126","author":"Darwich","year":"2009","journal-title":"Immunology"},{"key":"2025032406582237600_r7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.cyto.2012.06.012","article-title":"Interferon-\u03b3, tumor necrosis factor, and interleukin-18 cooperate to control growth of Mycobacterium tuberculosis in human macrophages","volume":"60","author":"Robinson","year":"2012","journal-title":"Cytokine"},{"key":"2025032406582237600_r8","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.4049\/jimmunol.1201528","article-title":"Cutting edge: a novel mechanism bridging innate and adaptive immunity: IL-12 induction of CD25 to form high-affinity IL-2 receptors on NK cells","volume":"189","author":"Lee","year":"2012","journal-title":"J. Immunol."},{"key":"2025032406582237600_r9","doi-asserted-by":"crossref","first-page":"406","DOI":"10.3109\/01902148.2012.716903","article-title":"IL-18 and IL-12 synergy induces matrix degrading enzymes in the lung","volume":"38","author":"Cero","year":"2012","journal-title":"Exp. Lung Res."},{"key":"2025032406582237600_r10","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1253\/circj.CJ-11-1338","article-title":"Interleukin-18 and interleukin-12 together downregulate ATP-binding cassette transporter A1 expression through the interleukin-18R\/nuclear factor-\u03baB signaling pathway in THP-1 macrophage-derived foam cells","volume":"76","author":"Yu","year":"2012","journal-title":"Circ. J."},{"key":"2025032406582237600_r11","doi-asserted-by":"crossref","first-page":"e1449","DOI":"10.1371\/journal.pntd.0001449","article-title":"IFN-\u03b3 production depends on IL-12 and IL-18 combined action and mediates host resistance to dengue virus infection in a nitric oxide-dependent manner","volume":"5","author":"Fagundes","year":"2011","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2025032406582237600_r12","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1189\/jlb.0306150","article-title":"Monocyte-derived macrophages and myeloid cell lines as targets of HIV-1 replication and persistence","volume":"80","author":"Cassol","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"2025032406582237600_r13","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.antiviral.2009.09.016","article-title":"HIV reservoirs, latency, and reactivation: prospects for eradication","volume":"85","author":"Dahl","year":"2010","journal-title":"Antiviral Res."},{"key":"2025032406582237600_r14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.antiviral.2009.09.009","article-title":"Novel approaches to inhibiting HIV-1 replication","volume":"85","author":"Adamson","year":"2010","journal-title":"Antiviral Res."},{"key":"2025032406582237600_r15","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/nature10195","article-title":"Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein","volume":"474","author":"Hrecka","year":"2011","journal-title":"Nature"},{"key":"2025032406582237600_r16","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nature10117","article-title":"SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx","volume":"474","author":"Laguette","year":"2011","journal-title":"Nature"},{"key":"2025032406582237600_r17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/ni.2236","article-title":"SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates","volume":"13","author":"Lahouassa","year":"2012","journal-title":"Nat. Immunol."},{"key":"2025032406582237600_r18","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.antiviral.2012.12.009","article-title":"Nucleotide embargo by SAMHD1: a strategy to block retroviral infection","volume":"97","author":"Pauls","year":"2013","journal-title":"Antiviral Res."},{"key":"2025032406582237600_r19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1189\/jlb.1106698","article-title":"Skewed expression and up-regulation of the IL-12 and IL-18 receptors in resting and activated CD4 T cells from HIV-1-infected patients","volume":"82","author":"de Arquer","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"2025032406582237600_r20","doi-asserted-by":"crossref","first-page":"464","DOI":"10.4049\/jimmunol.1002693","article-title":"\u03b25 integrin is the major contributor to the \u03b1V integrin-mediated blockade of HIV-1 replication","volume":"186","author":"Ballana","year":"2011","journal-title":"J. Immunol."},{"key":"2025032406582237600_r21","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1182\/blood-2008-06-161869","article-title":"Cell adhesion through \u03b1V-containing integrins is required for efficient HIV-1 infection in macrophages","volume":"113","author":"Ballana","year":"2009","journal-title":"Blood"},{"key":"2025032406582237600_r22","doi-asserted-by":"crossref","first-page":"9301","DOI":"10.1128\/JVI.01006-10","article-title":"Exploiting drug repositioning for discovery of a novel HIV combination therapy","volume":"84","author":"Clouser","year":"2010","journal-title":"J. Virol."},{"key":"2025032406582237600_r23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/mthe.2002.0541","article-title":"High levels of transduction of human dendritic cells with optimized SIV vectors","volume":"5","author":"Mangeot","year":"2002","journal-title":"Mol. Ther."},{"key":"2025032406582237600_r24","doi-asserted-by":"crossref","first-page":"8773","DOI":"10.1128\/JVI.01044-12","article-title":"Antiretroviral agents effectively block HIV replication after cell-to-cell transfer","volume":"86","author":"Permanyer","year":"2012","journal-title":"J. Virol."},{"key":"2025032406582237600_r25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0165-2478(00)00276-5","article-title":"Identification of human homologue of mouse IFN-\u03b3 induced protein from human dendritic cells","volume":"74","author":"Li","year":"2000","journal-title":"Immunol. Lett."},{"key":"2025032406582237600_r26","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1126\/science.8097338","article-title":"Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages","volume":"260","author":"Hsieh","year":"1993","journal-title":"Science"},{"key":"2025032406582237600_r27","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1046\/j.1365-2249.2003.02271.x","article-title":"Evidence for increased expression of regulatory cytokine receptors interleukin-12R and interleukin-18R in common variable immunodeficiency","volume":"134","author":"McQuaid","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"2025032406582237600_r28","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1084\/jem.188.8.1485","article-title":"Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells","volume":"188","author":"Xu","year":"1998","journal-title":"J. Exp. Med."},{"key":"2025032406582237600_r29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.4049\/jimmunol.167.1.221","article-title":"Positive regulatory role of IL-12 in macrophages and modulation by IFN-\u03b3","volume":"167","author":"Grohmann","year":"2001","journal-title":"J. Immunol."},{"key":"2025032406582237600_r30","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1038\/nm.2964","article-title":"SAMHD1 restricts HIV-1 infection in resting CD4+ T cells","volume":"18","author":"Baldauf","year":"2012","journal-title":"Nat. Med."},{"key":"2025032406582237600_r31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1742-4690-9-87","article-title":"SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+ T-cells","volume":"9","author":"Descours","year":"2012","journal-title":"Retrovirology"},{"key":"2025032406582237600_r32","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/ng.373","article-title":"Mutations involved in Aicardi-Gouti\u00e8res syndrome implicate SAMHD1 as regulator of the innate immune response","volume":"41","author":"Rice","year":"2009","journal-title":"Nat. Genet."},{"key":"2025032406582237600_r33","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2010.11.001","article-title":"Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue","volume":"143","author":"Doitsh","year":"2010","journal-title":"Cell"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/190\/9\/4736\/62501861\/1203226.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/190\/9\/4736\/62501861\/1203226.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T07:29:32Z","timestamp":1742974172000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/190\/9\/4736\/8004190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,1]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,5,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1203226","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,5]]},"published":{"date-parts":[[2013,5,1]]}}}