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Hum. Reprod. Advance Access originally published online on March 10, 2006
Human Reproduction 2006 21(5):1135-1142; doi:10.1093/humrep/dei496
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Seminal plasma promotes the attraction of Langerhans cells via the secretion of CCL20 by vaginal epithelial cells: involvement in the sexual transmission of HIV

W. Berlier, M. Cremel, H. Hamzeh, R. Lévy, F. Lucht, T. Bourlet, B. Pozzetto and O. Delézay1

GIMAP, Groupe Immunité des Muqueuses et Agents Pathogènes, Faculté de Médecine J. Lisfranc, Saint Etienne, France

1 To whom correspondence should be addressed at: GIMAP, Faculté de Médecine Jacques Lisfranc, 42023 Saint-Etienne cedex 02, France. E-mail: delezay{at}univ-st-etienne.fr

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 3{alpha} (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. METHODS AND 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-{kappa}B 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.

Key words: CCL20/HIV/Langerhans cell/semen/vaginal mucosa


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