Semen clusterin is a novel soluble DC-SIGN ligand

J. SABATTÉ; W. FAIGLE; A. CEBALLOS; W. MORELLE; C. RODRIGUEZ RODRIGUES; F. REMES LENICOV; M. THÉPAUT; F. FIESCHI; E. MALCHIODI; M. FERNANDEZ; F. AREZANA-SEISDEDOS; H. LORTAT-JACOB; J.-C. MICHALSKI; J. GEFFNER; S. AMIGORENA

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2011 vol. 187 p. 5299 - 5309

0022-1767

The C-type lectin receptor dendritic cell-specific ICAM-3?grabbing nonintegrin (DC-SIGN) is an important player in the recognitionof pathogens by dendritic cells. A plethora of pathogens including viruses, bacteria, parasites, and fungi are recognized byDC-SIGN through both mannose and fucose-containing glycans expressed on the pathogen surface. In this study, we identifiedsemen clusterin as a novel DC-SIGN ligand. Semen clusterin, but not serum clusterin, expresses an extreme abundance of fucosecontainingblood-type Ags such as Lex and Ley, which are both excellent DC-SIGN ligands. These motifs enable semen clusterin tobind DC-SIGN with very high affinity (Kd 76 nM) and abrogate the binding of HIV-1 to DC-SIGN. Depletion of clusterin fromsemen samples, however, did not completely prevent the ability of semen to inhibit the capture of HIV-1 by DC-SIGN, supportingthat besides clusterin, semen contains other DC-SIGN ligands. Further studies are needed to characterize these ligands and definetheir contribution to the DC-SIGN?blocking activity mediated by semen. Clusterin is an enigmatic protein involved in a variety ofphysiologic and pathologic processes including inflammation, atherosclerosis, and cancer. Our results uncover an unexpectedheterogeneity in the glycosylation pattern of clusterin and suggest that the expression of high concentrations of fucose-containingglycans enables semen clusterin to display a unique set of biological functions that might affect the early course of sexuallytransmitted infectious diseases. The Journal of Immunology, 2011, 187: 5299?5309.