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PD-1 has two ligands: PD-L1, expressed on hematopoietic and nonhematopoietic cells, and PD-L2, limited to DCs and macrophages. Little is known about PD-L1 expression and regulation in human macrophages. Previous reports have found few immediate effects of macrophage exposure to HIV, suggesting that macrophages lack PRRs for this virus. Using quantitative confocal microscopy and a multiplexed cytokine bead array, we measured induction of PD-L1, PD-L2, and innate response cytokines in human MDMs in response to chemically inactivated HIV virions. Consistent with previous reports, no cytokines were induced by HIV virion exposure. Whereas PD-L1 and PD-L2 had low baseline expression, TLR ligands (LPS and CL097) up-regulated PD-L1 but not PD-L2. Unlike what we found for cytokine expression, PD-L1 and PD-L2 were up-regulated in response to exposure with inactivated HIV virions or with replication-competent HIV. Expression of PD-L1 was differentially modulated by IL-10, which induced up-regulation of PD-L1 but not of PD-L2, and IL-10 blockade enhanced only PD-L2 expression. We discuss implications for innate recognition of HIV by macrophages and potential, different roles for PD-L1 and PD-L2 in immunity and pathogenesis.<\/jats:p>","DOI":"10.1189\/jlb.0610327","type":"journal-article","created":{"date-parts":[[2010,11,20]],"date-time":"2010-11-20T03:47:04Z","timestamp":1290224824000},"page":"507-515","source":"Crossref","is-referenced-by-count":89,"title":["Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10"],"prefix":"10.1093","volume":"89","author":[{"given":"Marta","family":"Rodr\u00edguez-Garc\u00eda","sequence":"first","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University , Charlestown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippos","family":"Porichis","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University , Charlestown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier G","family":"de Jong","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University , Charlestown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Levi","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University , Charlestown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Diefenbach","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University , Charlestown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D","family":"Lifson","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, SAIC Frederick Inc., National Cancer Institute at Frederick , Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon J","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana Farber Cancer Center, Department of Medicine, Harvard Medical School , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D","family":"Walker","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University , Charlestown, Massachusetts, USA"},{"name":"Howard Hughes Medical Institute , Charlestown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University , Charlestown, Massachusetts, USA"},{"name":"Division of Infectious Diseases, Massachusetts General Hospital , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University , Charlestown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,11,19]]},"reference":[{"key":"2023032914013610900_","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev.micro.62.081307.162758","article-title":"Cell biology of HIV-1 infection of macrophages","volume":"62","author":"Carter","year":"2008","journal-title":"Annu. 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