Modulation of HIV Binding to Epithelial Cells and HIV Transfer from Immature Dendritic Cells to CD4 T Lymphocytes by Human Lactoferrin and its Major Exposed LF-33 Peptide
Laetitia Carthagena1, ө, §, Pierre Becquart1, 2, §, Hakim Hocini3, Michel D Kazatchkine4, Hicham Bouhlal1, 5, Laurent Belec*, 1, 4
1 Inserm U743/Team « Immunité et Biothérapie Muqueuse », Paris, France
2 MIVEGEC (IRD 224 - CNRS 5290 - Universités Montpellier 1&2), Institut de Recherche pour le Développement & Centre National pour la Recherche Scientifique & Université Montpellier I, Montpellier, France
3 Institut National de la Santé et de la Recherche Médicale UMR-S 945, France
4 Hôpital Européen Georges Pompidou, Paris, and Université Paris Descartes, Paris V, France
5 Université Jules Verne Picardie, Inserm U925, Faculté de Médecine, Amiens, France
Current address: Unité Inserm 996 - Cytokines, Chimiokines et immunopathologie, 92140 Clamart Cedex, France
Lactoferrin (LF), a multifunctional molecule present in human secretions, has potent inhibitory activities against human immunodeficiency virus (HIV). The aim of the study was to evaluate whether human LF (hLF) and its exposed domain LF-33 represented by the peptide (LF-33-GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGP) involved in LF-HIV gag binding and endotoxines neutralization, may inhibit early steps of HIV mucosal transmission. Human LF and the peptide LF-33 inhibited the attachment of primary X4-tropic HIV-1NDK and R5-tropic HIV-1JR-CSF strains to human endometrial (HEC-1) and colorectal (HT-29) CD4-negative epithelial cells, the purified hLF being more potent (up to 80%) than the LF-33 peptide. In addition, the hLF, but not the LF-33 peptide, inhibited up to 40% the transfer in trans of HIV-1JR-CSF and HIV-1NDK, from immature dendritic cells to CD4 T lymphocytes, likely in a DC-SIGN-dependent manner. Altogether, these findings demonstrate that hLF can interfere with HIV-1 mucosal transmission by blocking virus attachment to epithelial cells and by inhibiting virus transfer from dendritic cells to CD4 T cells, two crucial steps of HIV dissemination from mucosae to lymphoid tissue.
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* Address correspondence to this author at the Hôpital Européen Georges Pompidou, and Université Paris Descartes (Paris V), 15-20 rue Leblanc, 75908 Paris Cedex 15, France; E-mail: email@example.com§Laetitia Carthagena and Pierre Becquart contributed equally to the work