Semen Clusterin Is a Novel DC-SIGN Ligand

被引：61

作者：

Sabatte, Juan ^{[1
,2
]}

Faigle, Wolfgang ^{[3
]}

Ceballos, Ana ^{[2
]}

Morelle, Willy ^{[4
]}

Rodriguez Rodrigues, Christian ^{[2
]}

Remes Lenicov, Federico ^{[2
]}

Thepaut, Michel ^{[5
]}

Fieschi, Franck ^{[5
]}

Malchiodi, Emilio

Fernandez, Marisa

Arenzana-Seisdedos, Fernando

Lortat-Jacob, Hugues ^{[5
]}

Michalski, Jean-Claude

Geffner, Jorge ^{[1
]}

Amigorena, Sebastian ^{[1
]}

机构：

[1] Inst Curie, INSERM, U653, F-75248 Paris, France

[2] Univ Buenos Aires, Fac Med, Ctr Nacl Referencia el SIDA, Dept Microbiol, RA-1121 Buenos Aires, DF, Argentina

[3] Inst Curie, Lab Prote Mass Spectrometry, F-75248 Paris, France

[4] Ctr Natl Rech Sci, Unite Mixte Rech 8576, Unite Glycobiol Struc & Fonct, F-59655 Villeneuve Dascq, France

[5] Univ Joseph Fourier 5075, Inst Biol Struct, Unite Mixte Rech, Ctr Nacl Referencia el SIDA Commissariat Energie, F-38027 Grenoble, France

来源：

JOURNAL OF IMMUNOLOGY | 2011年 / 187卷 / 10期

关键词：

HUMAN SEMINAL PLASMA; SEXUALLY-TRANSMITTED-DISEASES; C-TYPE LECTINS; DENDRITIC CELLS; EXTRACELLULAR CHAPERONE; MASS-SPECTROMETRY; IMMUNE-RESPONSES; T-CELLS; PROTEIN; GLYCOSYLATION;

D O I：

10.4049/jimmunol.1101889

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The C-type lectin receptor dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is an important player in the recognition of pathogens by dendritic cells. 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. In this study, 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 Ags such as Le(x) and Le(y), which are both excellent DC-SIGN ligands. These motifs enable semen clusterin to bind DC-SIGN with very high affinity (K(d) 76 nM) and 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 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. The Journal of Immunology, 2011, 187: 5299-5309.

引用

页码：5299 / 5309

页数：11