The levels of DNGR-1 and its ligand-bearing cells were altered after human and simian immunodeficiency virus infection
Abstract
Dendritic cell NK lectin Group Receptor-1 (DNGR-1), also known as C-type lectin domain family 9, member A (CLEC9A), is a member of C-type lectin receptor superfamily expressed primarily on dendritic cells (DC) that excel in cross-presentation of exogenous antigens. To find out whether and how it is affected in human immunodeficiency virus infections or acquired immunodeficiency syndromes (HIV/AIDS), DNGR-1 expression and DNGR-1-binding cells in simian/human immunodeficiency virus (SHIV) and simian immunodeficiency virus (SIV)-infected rhesus macaques and antiretroviral therapy (ART)-treated AIDS patients were examined by real-time RT-PCR, flow cytometry, and confocal microscopy. DNGR-1 expression was observed in both lymphoid and non-lymphoid tissues including gut-associated lymphoid tissues (GALT) of rhesus macaques. DNGR-1 mRNA levels were significantly reduced in the blood while significantly elevated in the GALT of SHIV/SIV-infected rhesus macaques. DNGR-1 transcription levels were also significantly reduced in the blood of ART-treated AIDS patients irrespective of viral status. White blood cells with exposed DNGR-1 ligands were significantly increased in ART-treated AIDS patients, while significantly decreased in SIV-infected rhesus macaques. These data indicate that DNGR-1 expression, and by extension, the function of cross-presentation of antigens associated with dead/damaged cells might be compromised in HIV/SIV infection, which might play a role in HIV/AIDS pathogenesis and should be taken into consideration in therapeutic AIDS vaccine development.
Keywords
DNGR-1 CLEC9A HIV-1 SHIV/SIV infection ART Rhesus macaquesNotes
Acknowledgements
The study was funded by MOST of China (Grant number 2013ZX10001004-002-001) and NNSF of China (Grant number 81571607). The authors would like to take the opportunity to express the appreciation to those who contributed the blood samples for this study.
Compliance with ethical standards
Conflict of interest
No competing financial interests exist.
Supplementary material
DNGR-1 immunoreactive cells in intestinal mucosa. DNGR-1 immunoreactive cells were detected with anti-rhDNGR-1 polyclonal antibody raised in our laboratory. TSA-tyramide signal amplification method was used. Images of DNGR-1 immunoreactivity (green), auto-fluoresence (mostly by macrophages, red), nuclei (blue) and DIC including cells with endogenous peroxidase activity (deep black) were obtained with laser scanning confocal microscope. Original amplification, 40× (GIF 83 kb)
Correlations between DNGR-1 mRNA levels and CD4 count in group V+R- and between DNGR-1 mRNA levels and plasma viral load in group V+R+. Data were log transformed and Pearson’s tests were performed. (GIF 17 kb)
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