Expression of human immunodeficiency virus (HIV)-binding lectin DC-SIGNR: Consequences for HIV infection and immunity.
DC-SIGNR is a human immunodeficiency virus (HIV)-binding C-type lectin that is expressed on endothelium in the hepatic sinusoids, lymph node sinuses and placenta. Like closely related DC-SIGN, DC-SIGNR can bind both ICAM-3 and HIV and can potentiate HIV infection of T lymphocytes in trans. In the present study we have investigated reasons underlying the restricted distribution of DC-SIGNR and have examined DC-SIGNR expression in relation to HIV entry receptors. We show that DC-SIGNR expression does not depend on endothelial cell specialization or on activation state. DC-SIGNR-positive endothelium continues to express DC-SIGNR in conditions of hyperplasia, whereas the molecule is lost after neoplastic transformation, most likely as a result of changes in the microenvironment of the endothelial cells. We have further shown that CCR5, but not CD4, is coexpressed with DC-SIGNR on hepatic sinusoidal and placental capillary endothelial cells. However, CD4-positive CCR5-positive cells, such as hepatic Kupffer cells, placental Hofbauer cells, and CD4-positive T lymphocytes in lymph nodes, can be found adjacent to DC-SIGNR-positive endothelium. Therefore, DC-SIGNR may be able to mediate HIV infection of these cells in trans. Finally, we demonstrate that DC-SIGN and DC-SIGNR can be coexpressed on lymph node sinus endothelial cells, which may lead to modulation of the function of both molecules.
Soilleux
Elizabeth J
EJ
Medical Research Council Cancer Centre Unit, Hutchison/MRC Research Centre, Cambridge, UK.
Morris
Lesley S
LS
Rushbrook
Simon
S
Lee
Benhur
B
Coleman
Nicholas
N
D000818:Animals; D014408:Biomarkers, Tumor; D015704:CD4 Antigens / Q000096:biosynthesis; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D002460:Cell Line; D002645:Chickens; D019040:E-Selectin / Q000032:analysis; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006684:HLA-DR Antigens / Q000032:analysis; D006391:Hemangioma / Q000150:complications / Q000473:pathology; D006801:Humans; D037102:Lectins / Q000096:biosynthesis*; D037181:Lectins, C-Type; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D010641:Phenotype; D011817:Rabbits; D019713:Receptors, CCR5 / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D013499:Surface Properties; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D014408:Biomarkers, Tumor; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D006684:HLA-DR Antigens; D037102:Lectins; D037181:Lectins, C-Type; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human