The DC-SIGNR 7/5 Genotype is Associated with High Dendritic Cell Counts and Their Subsets in Patients Infected with HIV-1

Chaudhary, Omkar; Bala, Manju; Singh, Vikram; Hazarika, Abhijit; Kumar, Rajesh; Luthra, Kalpana

doi:10.1007/s10875-013-9868-3

Cited by 4 publications

(1 citation statement)

References 31 publications

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“…Further, subsets of mDCs, i.e., BDCA-3 + DCs and BDCA-1 + DCs have been described ( 19 , 20 ). In HIV-1-infected individuals, a reduction in circulating mDC subsets and pDCs has been shown earlier ( 19 , 21 ). Decrease in mDC subsets has also been observed during advanced SIV infection ( 22 ).…”

Section: Introductionmentioning

confidence: 61%

Alterations in B Cell Compartment Correlate with Poor Neutralization Response and Disease Progression in HIV-1 Infected Children

et al. 2017

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Several B cell defects are reported in HIV-1 infected individuals including variation in B cell subsets, polyclonal B cell activation and exhaustion, with broadly neutralizing antibodies elicited in less than 10–20% of the infected population. HIV-1 disease progression is faster in children than adults. B Lymphocyte Stimulator (BLyS), expressed on dendritic cells (DCs), is a key regulator of B cell homeostasis. Understanding how DCs influence B cell phenotype and functionality (viral neutralization), thereby HIV-1 disease outcome in infected children, is important to develop interventional strategies for restoration of B cell function. In this study, a total of 38 vertically transmitted HIV-1 infected antiretroviral therapy (ART) naïve children and 25 seronegative controls were recruited. Based on the CD4 counts and years post-infection, infected children were categorized as long-term non-progressors (LTNPs) (n = 20) and progressors (n = 18). Eight of these progressors were followed up at 6–12 months post-ART. Percentages (%) of DCs, B cell subsets, and expression of BLyS on DCs were analyzed by flow-cytometry. Plasma levels of B cell growth factors were measured by ELISA and viral neutralization activity was determined using TZM-bl assay. Lower (%) of myeloid DCs (mDCs), plasmacytoid DCs, and high expression of BLyS on mDCs were observed in HIV-1 infected progressors than seronegative controls. Progressors showed lower % of naive B cells, resting memory B cells and higher % of mature activated, tissue-like memory B cells as compared to seronegative controls. Higher plasma levels of IL-4, IL-6, IL-10, and IgA were observed in progressors vs. seronegative controls. Plasma levels of IgG were high in progressors and in LTNPs than seronegative controls, suggesting persistence of hypergammaglobulinemia at all stages of disease. High plasma levels of BLyS in progressors positively correlated with poor viral neutralizing activity. Interestingly on follow up, treatment naïve progressors, post-ART showed increase in resting memory B cells along with reduction in plasma BLyS levels that correlated with improvement in viral neutralization. This is the first study to demonstrate that reduction in plasma BLyS levels correlates with restoration of B cell function, in terms of viral neutralization in HIV-1-infected children.

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Section: Introductionmentioning

confidence: 61%

Alterations in B Cell Compartment Correlate with Poor Neutralization Response and Disease Progression in HIV-1 Infected Children

et al. 2017

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Expression of complement receptor 3 (CR3) and regulatory protein CD46 on dendritic cells of antiretroviral naïve and treated HIV-1 infected individuals: Correlation with immune activation status

Mishra

Mohata

Aggarwal

et al. 2018

Molecular Immunology

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Association of DC-SIGNR Expression in Peripheral Blood Mononuclear Cells with DC-SIGNR Genotypes in HIV-1 Infection

et al. 2015

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Dendritic cell-specific intracellular adhesion molecule 3 grabbing nonintegrin related molecule (DC-SIGNR) is a C-type lectin, calcium-dependent carbohydrate-binding protein, which can act as a cell-adhesion and pathogen recognition receptor. DC-SIGNR is known to be highly expressed on liver sinusoidal cells and in the lymph nodes. However, its expression in peripheral blood mononuclear cells (PBMCs) in HIV-1 infection has not been addressed. Therefore, this study determined the expression of DC-SIGNR in PBMCs of HIV-1-infected patients and healthy seronegative individuals by real-time polymerase chain reaction and assessed its correlation with CD4+ T cell counts and DC-SIGNR genotypes. A significantly higher expression of DC-SIGNR was observed in the PBMCs of HIV-1-infected patients compared with healthy seronegative individuals. Further, there was a negative correlation between DC-SIGNR expression and CD4+ T cell counts and positive with viral load, with higher DC-SIGNR expression in the PBMCs of HIV-1-infected patients with a CD4+ T cell count <200 cells/μL than those with >200 cells/μL. This is the first study to report the expression of DC-SIGNR in PBMCs of HIV-1-infected patients. A salient finding of this study is that the DC-SIGNR expression was higher in HIV-1-infected patients, and its positive correlation with viral load and negative with CD4+ T cells counts suggesting a potential role of DC-SIGNR in HIV-1 infection.

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The DC-SIGNR 7/5 Genotype is Associated with High Dendritic Cell Counts and Their Subsets in Patients Infected with HIV-1

Abstract: This is the first study to assess the DC subsets and its association with DC-SIGNR polymorphism in injecting drug users and HIV-1 infected patients and suggests the protective role of 7/5 DC-SIGNR genotypes in HIV-1 infection.

Cited by 4 publications

References 31 publications

Alterations in B Cell Compartment Correlate with Poor Neutralization Response and Disease Progression in HIV-1 Infected Children

Alterations in B Cell Compartment Correlate with Poor Neutralization Response and Disease Progression in HIV-1 Infected Children

Expression of complement receptor 3 (CR3) and regulatory protein CD46 on dendritic cells of antiretroviral naïve and treated HIV-1 infected individuals: Correlation with immune activation status

Association of DC-SIGNR Expression in Peripheral Blood Mononuclear Cells with DC-SIGNR Genotypes in HIV-1 Infection

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