Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals

Casanova, Víctor, Naval-Macabuhay, Isaac, Massanella, Marta, Rodríguez-García, Marta, Blanco, Julià, Gatell, José M., García, Felipe, Gallart, Teresa, Lluis, Carme, Mallol, Josefa, Franco, Rafael, Climent, Núria and McCormick, Peter J (2012) Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals. PLoS One, 7 (12). ISSN 1932-6203

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Abstract

ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of ADA are implicated in the enhancement of CD80, CD83, CD86, CD40 and CCR7 expression on immature dendritic cells from healthy and HIV-infected individuals. These ADA-mediated increases in CD83 and costimulatory molecule expression is concomitant to an enhanced IL-12, IL-6, TNF-α, CXCL8(IL-8), CCL3(MIP1-α), CCL4(MIP-1β) and CCL5(RANTES) cytokine/chemokine secretion both in healthy and HIV-infected individuals and to an altered apoptotic death in cells from HIV-infected individuals. Consistently, ADA-mediated actions on iDCs are able to enhance allogeneic CD4 and CD8-T-cell proliferation, globally yielding increased iDC immunogenicity. Taken together, these findings suggest that ADA would promote enhanced and correctly polarized T-cell responses in strategies targeting asymptomatic HIV-infected individuals.

Item Type:	Article
Additional Information:	© 2012 Casanova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords:	adenosine deaminase,adult,aged,cd4-positive t-lymphocytes,cd8-positive t-lymphocytes,cell differentiation,cell proliferation,cells, cultured,cytokines,dendritic cells,female,hiv infections,hiv-1,humans,immunity,lymphocyte activation,male,middle aged,receptors, purinergic p1,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Pharmacy
Depositing User:	Pure Connector
Date Deposited:	13 Jan 2014 13:08
Last Modified:	24 Oct 2022 05:56
URI:	https://ueaeprints.uea.ac.uk/id/eprint/47147
DOI:	10.1371/journal.pone.0051287

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