Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/15887
Título: Major depletion of plasmacytoid dendritic cells in HIV-2 infection, an attenuated form of HIV disease.
Autor: Cavaleiro, R.
Baptista, A. P.
Soares, R. S.
Tendeiro, R.
Foxall, R. B.
Gomes, P.
Victorino, R. M.
Sousa, A. E.
Data: 2009
Editora: Public Library of Science
Citação: PLoS ONE November 2009 | Volume 5 | Issue 11 | e1000667
Resumo: Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-alpha production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although having the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4 decline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating pDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the undetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on circulating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC depletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral infection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of IFN-alpha production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in vitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-alpha inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-alpha levels were not elevated in HIV-2 infected individuals. In conclusion, our data in this unique natural model of "attenuated" HIV immunodeficiency contribute to the understanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion of circulating pDC in association with a relatively preserved IFN-alpha production does occur.
Descrição: © 2009 Cavaleiro 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.
Peer review: yes
URI: http://dx.doi.org/10.1371/journal.ppat.1000667
http://hdl.handle.net/10451/15887
ISSN: 1932-6203
Aparece nas colecções:IMM - Artigos em Revistas Internacionais
FM-LIC - Artigos em Revistas Internacionais

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