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Glycodendrimers prevent HIV transmission via DC-SIGN on dendritic cells
- Source :
- Garcia Vallejo, J J, Koning, N, Ambrosini, M, Kalay, H, Vuist, I, Sarrami-Forooshani, R, Geijtenbeek, T B H & van Kooyk, Y 2013, ' Glycodendrimers prevent HIV transmission via DC-SIGN on dendritic cells ', International Immunology, vol. 25, no. 4, pp. 221-233 . https://doi.org/10.1093/intimm/dxs115, International immunology, 25(4), 221-233. Oxford University Press, International Immunology, 25(4), 221-233. Oxford University Press
- Publication Year :
- 2013
-
Abstract
- Dendritic cells (DCs) are antigen-presenting cells efficient in capturing pathogens, and processing their antigenic determinants for presentation to antigen-specific T cells to induce robust immune responses. Their location at peripheral tissues and the expression of pattern-recognition receptors, among them DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), facilitates the capture of pathogens before spreading. However, some pathogens have developed strategies to escape the immune system. One of the most successful is HIV-1, which targets DC-SIGN for transport to the lymph node where the virus infects CD4(+) T cells. Contact of HIV-1 with DC-SIGN is thus the first event in the pathogenic cascade and, therefore, it is the primary target point for therapies aimed at HIV infection prevention. DC-SIGN recognizes specific glycans on HIV-1 and this interaction can be blocked by competitive inhibition through glycans. Although the affinity of glycans is relatively low, multivalency may increase avidity and the strength to compete with HIV-1 virions. We have designed multivalent dendrimeric compounds based on Lewis-type antigens that bind DC-SIGN with high selectivity and avidity and that effectively block gp120 binding to DC-SIGN and, consequently, HIV transmission to CD4(+) T cells. Binding to DC-SIGN and gp120 inhibition was higher on glycodendrimers with larger molecular diameter, indicating that the geometry of the compounds is an important factor determining their functionality. Our compounds elicited DC-SIGN internalization, a property of the receptor upon triggering, but did not affect the maturation status of DCs. Thus, Le(X) glycodendrimers could be incorporated into topic prophylactic approaches for the prevention of HIV-1 transmission.
- Subjects :
- Dendrimers
media_common.quotation_subject
Immunology
HIV Infections
Receptors, Cell Surface
Biology
HIV Envelope Protein gp120
Binding, Competitive
Structure-Activity Relationship
Immune system
Lewis Blood Group Antigens
Antigen
Polysaccharides
Immunology and Allergy
Humans
Avidity
Lectins, C-Type
Molecular Targeted Therapy
Receptor
Antigen-presenting cell
Internalization
Cells, Cultured
media_common
Immune Evasion
Cell Differentiation
General Medicine
T lymphocyte
Dendritic Cells
Virus Internalization
Virology
DC-SIGN
biology.protein
HIV-1
Cell Adhesion Molecules
Subjects
Details
- ISSN :
- 09538178
- Database :
- OpenAIRE
- Journal :
- Garcia Vallejo, J J, Koning, N, Ambrosini, M, Kalay, H, Vuist, I, Sarrami-Forooshani, R, Geijtenbeek, T B H & van Kooyk, Y 2013, ' Glycodendrimers prevent HIV transmission via DC-SIGN on dendritic cells ', International Immunology, vol. 25, no. 4, pp. 221-233 . https://doi.org/10.1093/intimm/dxs115, International immunology, 25(4), 221-233. Oxford University Press, International Immunology, 25(4), 221-233. Oxford University Press
- Accession number :
- edsair.doi.dedup.....019014cc1da025f174586d1db9df40a6