Naidoo, Kewreshini K;
Shangase, Zesuliwe B;
Rashid, Tabassum;
Ngubane, Ayanda;
Ismail, Nasreen;
Ndung'u, Thumbi;
Thobakgale, Christina F;
(2020)
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
, 15
(11)
, Article e0242448. 10.1371/journal.pone.0242448.
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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.
| Type: | Article |
|---|---|
| Title: | The DARC-null trait is associated with moderate modulation of NK cell profiles and unaltered cytolytic T cell profiles in black South Africans |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0242448 |
| Publisher version: | https://doi.org/10.1371/journal.pone.0242448 |
| Language: | English |
| Additional information: | © 2020 Naidoo 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. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, NATURAL-KILLER-CELLS, DUFFY ANTIGEN RECEPTOR, HUMAN-IMMUNODEFICIENCY-VIRUS, HIV-INFECTION, DISEASE PROGRESSION, NEUTROPHIL COUNTS, ACTIVATION, EXPRESSION, INNATE, BLOOD |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10149507 |
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