Seminal plasma promotes the attraction of Langerhans cells via the secretion of CCL20 by vaginal epithelial cells: involvement in the sexual transmission of HIV.
BACKGROUND
Heterosexual human immunodeficiency virus (HIV) transmission implies the crossing of the vaginal mucosa by virions present in the semen, potentially using Langerhans cells as transporters. The recruitment of these cells in the mucosa is mediated by the chemokine macrophage inflammatory protein 3alpha (CCL20). The aim of this study was to evaluate the capacity of the semen to induce Langerhans cell recruitment via the production of CCL20 by vaginal epithelial cells.


RESULTS
Using a vaginal epithelium model based on the SiHa cell line and human seminal plasma, we demonstrated that semen enhanced the production of CCL20. This secretion was regulated by the nuclear factor-kappaB intracellular signalling pathway. Fractionation of the seminal plasma indicated that the secretion of CCL20 was stimulated by high molecular weight compounds present in semen. Migration assays demonstrated that secreted CCL20 was able to promote the recruitment of Langerhans cell precursors (LCps), which remain permissive to X4 and R5 HIV infection.


CONCLUSIONS
Our results demonstrate that epithelial cells respond to factors present in semen by secreting CCL20, leading to the enhancement of LCp recruitment. These data argue in favour of the implication of epithelial cells in the heterosexual transmission of HIV.
GIMAP, Groupe Immunité des Muqueuses et Agents Pathogènes, Faculté de Médecine J. Lisfranc, Saint Etienne, France.
W
W
Berlier
M
M
Cremel
H
H
Hamzeh
R
R
Lévy
F
F
Lucht
T
T
Bourlet
B
B
Pozzetto
O
O
Delézay
D002465:Cell Movement / Q000276:immunology; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D012661:Semen / Q000276:immunology*; D015229:Sexually Transmitted Diseases, Viral / Q000276:immunology / Q000635:transmission*; D015398:Signal Transduction; D014621:Vagina / Q000166:cytology / Q000276:immunology*
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B