INVESTIGADORES
MALCHIODI Emilio Luis
artículos
Título:
Semen clusterin is a novel DC-SIGN ligand
Autor/es:
JUAN SABATTE; WOLFGANG FAIGLE; ANA CEBALLOS; WILLY MORELLE; CHRISTIAN RODRÍGUEZ RODRÍGUES; FEDERICO REMES LENICOV; MICHEL THÉPAUT; FRANCK FIESCHI; EMILIO MALCHIODI; MARISA FERNÁNDEZ; FERNANDO ARENZANA-SEISDEDOS; HUGUES LORTAT-JACOB; JEAN-CLAUDE MICHALSKI; JORGE GEFFNER; SEBASTIAN AMIGORENA
Revista:
JOURNAL OF IMMUNOLOGY
Editorial:
AMER ASSOC IMMUNOLOGISTS
Referencias:
Año: 2011 vol. 187 p. 5299 - 5309
ISSN:
0022-1767
Resumen:
The C-type lectin receptor DC-SIGN is an important player in the recognition of pathogens by dendritic cells (DCs). A plethora of pathogens including viruses, bacteria, parasites, and fungi are recognized by DC-SIGN through both mannose and fucose-containing glycans expressed on the pathogen surface. Here, we identified semen clusterin as a novel DC-SIGN ligand. Semen clusterin, but not serum clusterin, expresses an extreme abundance of fucose-containing blood-type antigens such as Lex and Ley, which are both excellent DC-SIGN ligands. These motifs enable semen clusterin to bind DC-SIGN with very high affinity (Kd=76 nM) and to abrogate the binding of HIV-1 to DC-SIGN. Depletion of clusterin from semen samples, however, did not completely prevent the ability of semen to inhibit the capture of HIV-1 by DC-SIGN, supporting that besides clusterin, semen contains other DC-SIGN-ligands. Further studies are needed to characterize these ligands and to define their contribution to the DC-SIGN blocking activity mediated by semen. Clusterin is an enigmatic protein involved in a variety of physiologic and pathologic processes including inflammation, atherosclerosis and cancer. Our results uncover an unexpected heterogeneity in the glycosylation pattern of clusterin and suggest that the expression of high concentrations of fucose-containing glycans enables semen clusterin to display a unique set of biological functions that might affect the early course of sexually transmitted infectious diseases. x and Ley, which are both excellent DC-SIGN ligands. These motifs enable semen clusterin to bind DC-SIGN with very high affinity (Kd=76 nM) and to abrogate the binding of HIV-1 to DC-SIGN. Depletion of clusterin from semen samples, however, did not completely prevent the ability of semen to inhibit the capture of HIV-1 by DC-SIGN, supporting that besides clusterin, semen contains other DC-SIGN-ligands. Further studies are needed to characterize these ligands and to define their contribution to the DC-SIGN blocking activity mediated by semen. Clusterin is an enigmatic protein involved in a variety of physiologic and pathologic processes including inflammation, atherosclerosis and cancer. Our results uncover an unexpected heterogeneity in the glycosylation pattern of clusterin and suggest that the expression of high concentrations of fucose-containing glycans enables semen clusterin to display a unique set of biological functions that might affect the early course of sexually transmitted infectious diseases.