Galactosyl ceramide expressed on dendritic cells can mediate HIV-1 transfer from monocyte derived dendritic cells to autologous T cells.
Mucosa, comprising epithelial and dendritic cells, are the major sites for Human Immunodeficiency Virus type 1 (HIV-1) transmission. There, DCs can capture incoming HIV-1 and in turn transfer virus to CD4(+) T lymphocytes in a two-phase process, thereby initiating HIV-1 dissemination. We show that the glycosphingolipid Galactosyl Ceramide (GalCer), acting as mucosal epithelial receptor for HIV-1, was expressed by human monocyte derived immature DCs (iDCs), human primary DCs isolated from blood and mucosal tissue and in situ on mucosal tissue and acts as HIV-1-gp41 receptor. Blocking both GalCer and CD4 with specific mAbs results in a >95% transfer inhibition of HIV-1 from human monocyte-derived iDCs to autologous resting T cells. GalCer interaction with HIV-1 controls the early infection-independent phase of HIV-1 transfer to T cells. Thus, GalCer appears as an initial receptor for HIV-1, common to both mucosal epithelial cells and iDCs.
Magérus-Chatinet
Aude
A
Entrée Muqueuse du VIH et immunité muqueuse (Mucosal entry of HIV-1 and mucosal immunity), Departement de Biologie Cellulaire (Cell Biology Department), Institut Cochin, CNRS, INSERM, Université René Descartes, 22 rue Mechain, 75014 Paris, France.
Yu
Huifeng
H
Garcia
Séverine
S
Ducloux
Elodie
E
Terris
Benoit
B
Bomsel
Morgane
M
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000821:virology*; D005699:Galactosylceramides / Q000096:biosynthesis* / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000821:virology; D011991:Receptors, Virus / Q000096:biosynthesis* / Q000502:physiology
D005699:Galactosylceramides; D015700:HIV Envelope Protein gp41; D011991:Receptors, Virus