title: Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10.
abstract: PD-1 plays an important role in T cell exhaustion during HIV infection. 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.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard University, 149 13th St., Charlestown, MA 02129, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodríguez-García
authors.forename: Filippos
authors.initials: F
authors.lastname: Porichis
authors.forename: Olivier G
authors.initials: OG
authors.lastname: de Jong
authors.forename: Karen
authors.initials: K
authors.lastname: Levi
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Diefenbach
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Kavanagh
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D013601:T-Lymphocytes / Q000187:drug effects; D014771:Virion; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; D008070:Lipopolysaccharides; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D016753:Interleukin-10