Virulent Treponema pallidum, lipoprotein, and synthetic lipopeptides induce CCR5 on human monocytes and enhance their susceptibility to infection by human immunodeficiency virus type 1.
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.
Sellati
T J
TJ
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Wilkinson
D A
DA
Sheffield
J S
JS
Koup
R A
RA
Radolf
J D
JD
Norgard
M V
MV
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
D054407:Chemokine CCL4; D018925:Chemokines; D008074:Lipoproteins; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4