title: Virulent Treponema pallidum, lipoprotein, and synthetic lipopeptides induce CCR5 on human monocytes and enhance their susceptibility to infection by human immunodeficiency virus type 1.
abstract: Treponema pallidum, its membrane lipoproteins, and synthetic lipoprotein analogues (lipopeptides) were each examined to determine whether they induced CCR5 expression on human peripheral blood mononuclear cells (PBMC). Reverse transcription-polymerase chain reaction for CCR5 gene transcripts, macrophage inflammatory protein (MIP)-1beta binding assays, and flow cytometry revealed that either T. pallidum, a representative treponemal lipoprotein, or a corresponding synthetic lipopeptide induced CCR5 on CD14 monocytes but not on CD3 lymphocytes. CXCR4, the coreceptor for T cell-tropic strains of human immunodeficiency virus type 1 (HIV-1), was not induced on PBMC by treponemes or by lipoproteins or lipopeptides. Consistent with these findings, T. pallidum, lipoprotein, and synthetic lipopeptide all promoted the entry of a macrophage-tropic, but not a T cell-tropic, strain of HIV-1 into monocytes. These combined results imply that T. pallidum and its constituent lipoproteins likely induce the expression of CCR5 on macrophages in syphilitic lesions, thereby enhancing transmission of macrophage-tropic HIV-1.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Sellati
authors.forename: D A
authors.initials: DA
authors.lastname: Wilkinson
authors.forename: J S
authors.initials: JS
authors.lastname: Sheffield
authors.forename: R A
authors.initials: RA
authors.lastname: Koup
authors.forename: J D
authors.initials: JD
authors.lastname: Radolf
authors.forename: M V
authors.initials: MV
authors.lastname: Norgard
mesh_terms: D000328:Adult; D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism; D015658:HIV Infections / Q000209:etiology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000821:virology; D011485:Protein Binding / Q000187:drug effects; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D013587:Syphilis / Q000150:complications; D014210:Treponema pallidum / Q000737:chemistry* / Q000472:pathogenicity
chemical_list: D054407:Chemokine CCL4; D018925:Chemokines; D008074:Lipoproteins; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4