Purpose Of Review: The causes of ethnic or benign neutropenia have long been unclear. Here, we discuss the emerging data on the causes and consequences of neutropenia and discuss the relevance of these data for African populations, in which the prevalence of neutropenia is high.
Recent Findings: Genetic deletion of the Duffy antigen receptor for chemokines (DARC-null genotype) has been identified as a major determinant for neutropenia. DARC acts as a receptor for Plasmodium vivax malaria and the DARC-null genotype has thus been positively selected among Africans; however, recent studies suggest that Duffy-null-linked neutropenia could increase the risk of HIV infection. Data are emerging that neutrophils are versatile cells that play a critical role not only in direct antimicrobial activity but also in priming and regulating the activity of other innate and adaptive immune cells. Therefore, we discuss here the imperative to better understand the causes, consequences, and the underlying mechanisms of neutropenia among Africans as a prerequisite for rational and optimal biomedical interventions to improve health outcomes.
Summary: Neutropenia among Africans, linked to the Duffy-null trait or otherwise, may have significant health consequences that remain largely undetermined and could have a significant impact on the pathogenesis of diseases.
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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
January 2021
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
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.
View Article and Find Full Text PDFNeutrophil Effector Functions Are Not Impaired in Duffy Antigen Receptor for Chemokines (DARC)-Null Black South Africans.
Front Immunol
September 2020
HIV Pathogenesis Programme, Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Neutrophils are well-recognized for their pathogen killing mechanisms and disorders of neutrophil count and function are associated with recurrent infections. The Duffy Antigen Receptor for Chemokines (DARC)-null genotype is predominant in sub-Saharan African ancestry populations and is the major genetic determinant of benign ethnic neutropenia which has been associated with increased risk of Human Immunodeficiency Virus (HIV)-1 acquisition and mother-to-child transmission. However, the impact of DARC-null-linked neutropenia on HIV disease progression remains controversial.
View Article and Find Full Text PDFCorrelation between 'ACKR1/DARC null' polymorphism and benign neutropenia in Yemenite Jews.
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Cancer Research Centre, Sheba Medical Centre, Tel Hashomer, Israel.
Neutrophil counts in persons of African origin.
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aHIV Pathogenesis Programme, Doris Duke Medical Research Institute bKwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa cRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Boston, Massachusetts, USA dMax Planck Institute for Infection Biology, Berlin, Germany.
Purpose Of Review: The causes of ethnic or benign neutropenia have long been unclear. Here, we discuss the emerging data on the causes and consequences of neutropenia and discuss the relevance of these data for African populations, in which the prevalence of neutropenia is high.
Recent Findings: Genetic deletion of the Duffy antigen receptor for chemokines (DARC-null genotype) has been identified as a major determinant for neutropenia.
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