The DARC-null trait is associated with moderate modulation of NK cell profiles and unaltered cytolytic T cell profiles in black South Africans

PLoS One. 2020 Nov 19;15(11):e0242448. doi: 10.1371/journal.pone.0242448. eCollection 2020.

Abstract

The Duffy Antigen Receptor for Chemokines (DARC)-null trait, common among persons of African descent and associated with lower absolute neutrophil counts (ANCs), may be linked to increased risk to certain infections including HIV-1 but the underlying causes are poorly understood. We hypothesized that DARC-null-linked neutropenia may negatively impact neutrophil immunoregulatory modulation of other immune cells such as natural killer (NK) and CD8+ T cells leading to altered phenotype, functionality and homeostatic activity of these immune cells. HIV-1 uninfected (n = 20) and HIV-1 chronically infected (n = 19) participants were assessed using multi-parametric flow cytometry to determine NK and CD8+ T cell counts, phenotypic profiles, and cytokine production and degranulation. Annexin V and carboxyfluorescein succinimidyl ester (CFSE) staining were used to examine NK cell survival and NK cell and CD8+ T cell proliferation respectively. Participants were genotyped for the DARC-null polymorphism using allelic discrimination assays and ANCs were measured by full blood count. In HIV uninfected individuals, a reduction of total NK cell counts was noted in the absence of DARC and this correlated with lower ANCs. HIV uninfected DARC-null subjects displayed a less mature NK cell phenotype. However, this did not translate to differences in NK cell activation or effector functionality by DARC state. Whilst HIV-1 infected subjects displayed NK cell profiling that is typical of HIV infection, no differences were noted upon DARC stratification. Similarly, CD8+ T cells from HIV infected individuals displayed phenotypic and functional modulation that is characteristic of HIV infection, but profiling was unaffected by the DARC-null variant irrespective of HIV status. Overall, the data suggests that the DARC-null polymorphism and lower ANCs does not impede downstream cytolytic cell priming and functionality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / blood
  • Anti-HIV Agents / therapeutic use
  • Black People / genetics*
  • Cell Division
  • Cell Survival
  • Cytokines / blood
  • Duffy Blood-Group System / genetics
  • Female
  • Genotype
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV-1
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / immunology*
  • Lymphocyte Count
  • Male
  • Polymorphism, Single Nucleotide*
  • Receptors, Cell Surface / deficiency*
  • Receptors, Cell Surface / genetics
  • South Africa
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Load
  • Young Adult

Substances

  • ACKR1 protein, human
  • Anti-HIV Agents
  • Cytokines
  • Duffy Blood-Group System
  • Receptors, Cell Surface