Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

PLoS Pathogens

Ana E. Sousa¹  Perpétua Gomes²  Rita Tendeiro³  Rui M. M. Victorino³  Russell B. Foxall³  Rita Cavaleiro³  Rui S. Soares³  António P. Baptista³ 

[1] Clínica Universitária de Medicina 2, Hospital de Santa Maria, Lisboa, Portugal;Laboratório de Biologia Molecular, Serviço de Medicina Transfusional, Hospital Egas Moniz, Lisboa, Portugal;Unidade de Imunologia Clínica, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal

关键词: HIV-2;    HIV-1;    Viremia;    T helper cells;    Cytotoxic T cells;    T cells;    Opportunistic infections;    HIV;   

DOI  :  10.1371/journal.ppat.1000667

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-α 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-α 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-α inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-α 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-α production does occur.

【 授权许可】

CC BY