| dc.creator |
Serrano-Gómez, Diego |
|
| dc.creator |
Martínez-Nuñez, Rocío T. |
|
| dc.creator |
Sierra-Filardi, Elena |
|
| dc.creator |
Izquierdo, Nuria |
|
| dc.creator |
Colmenares, María |
|
| dc.creator |
Pla, Jesús |
|
| dc.creator |
Rivas, Luis |
|
| dc.creator |
Martinez-Picado, Javier |
|
| dc.creator |
Jiménez-Barbero, Jesús |
|
| dc.creator |
Alonso-Lebrero, José Luis |
|
| dc.creator |
González, Salvador |
|
| dc.creator |
Corbí, Angel L. |
|
| dc.date |
2008-02-06T13:08:49Z |
|
| dc.date |
2008-02-06T13:08:49Z |
|
| dc.date |
2007-04-23 |
|
| dc.date.accessioned |
2017-01-31T00:59:58Z |
|
| dc.date.available |
2017-01-31T00:59:58Z |
|
| dc.identifier |
PMCID: 1913256 |
|
| dc.identifier |
Antimicrobial Agents and Chemotherapy 2007 July; 51(7): 2313–2323 |
|
| dc.identifier |
0066-4804 |
|
| dc.identifier |
http://hdl.handle.net/10261/2878 |
|
| dc.identifier |
10.1128/AAC.01289-06 |
|
| dc.identifier.uri |
http://dspace.mediu.edu.my:8181/xmlui/handle/10261/2878 |
|
| dc.description |
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. |
|
| dc.description |
This work was supported by the Ministerio de Educación y Ciencia (grants SAF2005-0021, AGL2004-02148-ALI, and GEN2003-20649-C06-01/NAC), the Fundación para la Investigación y Prevención del SIDA en España (grant FIPSE 36422/03), the Fundación de Investigación Médica Mutua Madrileña (grant 20060789), and the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Spanish Network for the Research in Infectious Diseases, grant REIPI RD06/0008), to A.L.C. and grant SAF2004-06991 to J.M.-P. D.S.-G. was supported by a predoctoral grant (grant AP2002-2151) from the Ministerio de Educación y Ciencia (Spain). R.T.M.-N. was funded by Beca de Introducción a la Investigación fellowship from the Consejo Superior de Investigaciones Científicas (CSIC). |
|
| dc.description |
Peer reviewed |
|
| dc.format |
630785 bytes |
|
| dc.format |
application/pdf |
|
| dc.language |
eng |
|
| dc.publisher |
American Society for Microbiology |
|
| dc.rights |
closedAccess |
|
| dc.title |
AM3 Modulates Dendritic Cell Pathogen Recognition Capabilities by Targeting DC-SIGN |
|
| dc.type |
Artículo |
|