Differential Modulation of Human Lactoferrin Activity against Both R5 and X4-HIV-1 Adsorption on Epithelial Cells and Dendritic Cells by Natural Antibodies

Human lactoferrin (Lf) is an iron binding glycoprotein that is present in several mucosal secretions. Many biological functions have been ascribed to Lf. In the present study, we showed that Lf limited specifically adsorption of R5- and X4-HIV-1-free particles on endometrial epithelial HEC-1A cells,...

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Published in:Journal of Immunology 2006-10, Vol.177 (8), p.5540-5549
Main Authors: Saidi, Hela, Eslaphazir, Jobin, Carbonneil, Cedric, Carthagena, Laetitia, Requena, Mary, Nassreddine, Nadine, Belec, Laurent
Format: Article
Language:English
Subjects:
Adsorption - drug effects
Anti-Infective Agents - chemistry
Antibodies - immunology
Body Fluids - immunology
Cell Line
Dendritic Cells - immunology
Epithelial Cells - immunology
Female
HIV-1 - drug effects
HIV-1 - immunology
Human immunodeficiency virus
Humans
Lactoferrin - immunology
Lactoferrin - pharmacology
Receptors, CCR5
Receptors, CXCR4
Vagina - immunology
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Summary:Human lactoferrin (Lf) is an iron binding glycoprotein that is present in several mucosal secretions. Many biological functions have been ascribed to Lf. In the present study, we showed that Lf limited specifically adsorption of R5- and X4-HIV-1-free particles on endometrial epithelial HEC-1A cells, by inhibiting virus adsorption on heparan-sulfated proteoglycans. But, Lf did not interfere with both R5 and X4-HIV transcytosis. We showed also the efficacy of Lf in preventing R5 and X4-HIV capture by dendritic cells. Conversely, we demonstrated that Lf-reacting natural Abs (NAbs) present within i.v. Ig-enhanced HIV attachment on dendritic cells by forming HIV-Lf-NAbs. HIV particles were able to directly interact with Lf following its interaction with NAbs. We also found Lf-reacting natural Abs within cervicovaginal secretions, suggesting the existence of Lf-NAbs complexes in women genital tract in vivo. In conclusion, this study highlights Lf as a potent microbicides and reports new function for NAbs within the genital compartment that may compartment that may abolish the inhibitory activity of microbicide compounds. Thus, we proposed a model in which Lf would appear as a double-edged sword that could have beneficial or detrimental effects depending on both cellular and molecular environments. This study highlights the use of Lf derivates as microbicide candidates to limit such interferences.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.177.8.5540