This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.01289-06v1 51/7/2313    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Serrano-Gómez, D. Articles by Corbí, A. L. Search for Related Content PubMed PubMed Citation Articles by Serrano-Gómez, D. Articles by Corbí, A. L.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2007, p. 2313-2323, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.01289-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

AM3 Modulates Dendritic Cell Pathogen Recognition Capabilities by Targeting DC-SIGN

Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain,¹ Facultad de Farmacia, Universidad Complutense, Madrid, Spain,² R&D Department, Industrial Farmacéutica Cantabria (IFC), Madrid, Spain,³ IrsiCaixa Foundation, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, and Institució Catalana de Recerra i Estudis Avançants (ICREA), Barcelona, Spain⁴

Received 17 October 2006/ Returned for modification 11 February 2007/ Accepted 17 April 2007

AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of Candida, Aspergillus, and Leishmania to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV trans-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and ¹D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities.

Published ahead of print on 23 April 2007.