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Université René Descartes Paris V, Unité Institut National de la Recherche et de la Santé (INSERM) Internationale 743 d’Immunologie Humaine, Equipe Immunité et Biothérapie Muqueuse, Centres de Recherches Biomédicales des Cordeliers, Paris, France
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 The study was supported by grants from the European Community (6th Framework, European Project on Microbicide Contract 503558) and from the Agence Nationale de Recherches sur le SIDA et les Hépatites (MultiMicro Project). Hela Saïdi was recipient of an EMPRO fellowship. Cédric Carbonneil was supported by the Agence Nationale de Recherches sur le AIDS et les Hépatites.
2 Address correspondence and reprint requests to Dr. Héla Saidi, Unité INSERM Internationale U743 (Immunologie Humaine), Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, 15, rue de l’Ecole de Médecine, 75270, Cedex 06, Paris, France. E-mail address: hela.saidi{at}u430.bhdc.jussieu.fr
3 Abbreviations used in this paper: HIV-1, HIV type 1; CVS, cervicovaginal secretion; DC, dendritic cell; HSPG, heparan sulfate proteoglycan; iMDCC, immature DC derived from monocyte; IVIg, i.v. Ig; KSCN, potassium thiocyanate Lf, human lactoferrin; NAb, natural Ab; PSA, prostatic soluble Ag; TER, transepithelial resistance.
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  J. Eslahpazir, M.-A. Jenabian, H. Bouhlal, H. Hocini, C. Carbonneil, G. Gresenguet, F.-X. M. Keou, J. LeGoff, H. Saidi, M. Requena, et al. Infection of Macrophages and Dendritic Cells with Primary R5-Tropic Human Immunodeficiency Virus Type 1 Inhibited by Natural Polyreactive Anti-CCR5 Antibodies Purified from Cervicovaginal Secretions Clin. Vaccine Immunol., May 1, 2008; 15(5): 872 - 884. [Abstract] [Full Text] [PDF]
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