Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.

<h4>Background</h4>Defensins are natural endogenous antimicrobial peptides with potent anti-HIV activity and immuno-modulatory effects. We recently demonstrated that immature dendritic cells (DC) produce alpha-defensins1-3 and that alpha-defensins1-3 modulate DC generation and maturation...

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Autores principales:	Marta Rodríguez-García, Núria Climent, Harold Oliva, Víctor Casanova, Rafael Franco, Agathe Leon, José M Gatell, Felipe García, Teresa Gallart
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/526a2652e57a4d728c8c794a805ccfde
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spelling	oai:doaj.org-article:526a2652e57a4d728c8c794a805ccfde2021-11-25T06:25:33ZIncreased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.1932-620310.1371/journal.pone.0009436https://doaj.org/article/526a2652e57a4d728c8c794a805ccfde2010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20195543/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Defensins are natural endogenous antimicrobial peptides with potent anti-HIV activity and immuno-modulatory effects. We recently demonstrated that immature dendritic cells (DC) produce alpha-defensins1-3 and that alpha-defensins1-3 modulate DC generation and maturation. Since DC-HIV interaction plays a critical role during the first steps of HIV infection, we investigated the possible impact of alpha-defensins1-3 production by DC on disease progression.<h4>Methodology/principal findings</h4>Monocyte-derived DC (MDDC) were analyzed comparatively in healthy controls (HC) and HIV-infected patients, including untreated "elite" and "viremic" controllers, untreated viremic non-controllers and antiretroviral-treated patients. We found that production of alpha-defensins1-3 was significantly increased in MDDC from HIV-infected patients versus HC, and this increase was mainly due to that observed in controllers, while in non-controllers the increase was not statistically significant (controllers vs. HC, p<0.005; controllers vs. non-controllers p<0.05). Secreted alpha-defensins1-3 by immature MDDC positively correlated with CD4 T cell counts in controllers, but not in non-controllers. Moreover, independently of their clinical classification, HIV-infected patients with higher alpha-defensins1-3 secretion by immature MDDC showed slower disease progression, measured as no decrease in the number of CD4+ T-cells below 350 cell/mm(3), lower increase of plasma viral load and no initiation of treatment over time. Plasma alpha-defensins1-3 levels lacked any relationship with immunologic and virologic parameters.<h4>Conclusions/significance</h4>High production of alpha-defensins1-3 by immature DCs appears as a host protective factor against progression of HIV-1 infection, suggesting potential diagnostic, therapeutic and preventive implications. This protective effect may arise from the activity of alpha-defensins1-3 to damage the virions prior and/or after their internalization by immature DC, and hence favoring a more efficient viral processing and presentation to HIV-specific CD4+ T cells, without or with a minor rate of transmission of infectious HIV-1 virions.Marta Rodríguez-GarcíaNúria ClimentHarold OlivaVíctor CasanovaRafael FrancoAgathe LeonJosé M GatellFelipe GarcíaTeresa GallartPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e9436 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marta Rodríguez-García Núria Climent Harold Oliva Víctor Casanova Rafael Franco Agathe Leon José M Gatell Felipe García Teresa Gallart Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.
description	<h4>Background</h4>Defensins are natural endogenous antimicrobial peptides with potent anti-HIV activity and immuno-modulatory effects. We recently demonstrated that immature dendritic cells (DC) produce alpha-defensins1-3 and that alpha-defensins1-3 modulate DC generation and maturation. Since DC-HIV interaction plays a critical role during the first steps of HIV infection, we investigated the possible impact of alpha-defensins1-3 production by DC on disease progression.<h4>Methodology/principal findings</h4>Monocyte-derived DC (MDDC) were analyzed comparatively in healthy controls (HC) and HIV-infected patients, including untreated "elite" and "viremic" controllers, untreated viremic non-controllers and antiretroviral-treated patients. We found that production of alpha-defensins1-3 was significantly increased in MDDC from HIV-infected patients versus HC, and this increase was mainly due to that observed in controllers, while in non-controllers the increase was not statistically significant (controllers vs. HC, p<0.005; controllers vs. non-controllers p<0.05). Secreted alpha-defensins1-3 by immature MDDC positively correlated with CD4 T cell counts in controllers, but not in non-controllers. Moreover, independently of their clinical classification, HIV-infected patients with higher alpha-defensins1-3 secretion by immature MDDC showed slower disease progression, measured as no decrease in the number of CD4+ T-cells below 350 cell/mm(3), lower increase of plasma viral load and no initiation of treatment over time. Plasma alpha-defensins1-3 levels lacked any relationship with immunologic and virologic parameters.<h4>Conclusions/significance</h4>High production of alpha-defensins1-3 by immature DCs appears as a host protective factor against progression of HIV-1 infection, suggesting potential diagnostic, therapeutic and preventive implications. This protective effect may arise from the activity of alpha-defensins1-3 to damage the virions prior and/or after their internalization by immature DC, and hence favoring a more efficient viral processing and presentation to HIV-specific CD4+ T cells, without or with a minor rate of transmission of infectious HIV-1 virions.
format	article
author	Marta Rodríguez-García Núria Climent Harold Oliva Víctor Casanova Rafael Franco Agathe Leon José M Gatell Felipe García Teresa Gallart
author_facet	Marta Rodríguez-García Núria Climent Harold Oliva Víctor Casanova Rafael Franco Agathe Leon José M Gatell Felipe García Teresa Gallart
author_sort	Marta Rodríguez-García
title	Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.
title_short	Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.
title_full	Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.
title_fullStr	Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.
title_full_unstemmed	Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.
title_sort	increased alpha-defensins 1-3 production by dendritic cells in hiv-infected individuals is associated with slower disease progression.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/526a2652e57a4d728c8c794a805ccfde
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Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.

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