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The role of the human Duffy antigen receptor for chemokines in malaria susceptibility: current opinions and future treatment prospects

Authors Ntumngia F, Thomson-Luque R, Pires C, Adams J

Received 15 July 2016

Accepted for publication 22 August 2016

Published 26 September 2016 Volume 2016:9 Pages 1—11

DOI https://doi.org/10.2147/JRLCR.S99725

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Professor Trevor W. Stone


Francis B Ntumngia,* Richard Thomson-Luque,* Camilla V Pires,* John H Adams

Department of Global Health, College of Public Health, University of South Florida, Tampa, FL, USA

*These authors contributed equally to this work.

Abstract: The Duffy antigen receptor for chemokine (DARC) is a nonspecific receptor for several proinflammatory cytokines. It is homologous to the G-protein chemokine receptor superfamily, which is suggested to function as a scavenger in many inflammatory-and proinflammatory-related diseases. G-protein chemokine receptors are also known to play a critical role in infectious diseases; they are commonly used as entry vehicles by infectious agents. A typical example is the chemokine receptor CCR5 or CXCR4 used by HIV for infecting target cells. In malaria, DARC is considered an essential receptor that mediates the entry of the human and zoonotic malaria parasites Plasmodium vivax and Plasmodium knowlesi into human reticulocytes and erythrocytes, respectively. This process is mediated through interaction with the parasite ligand known as the Duffy binding protein (DBP). Most therapeutic strategies have been focused on blocking the interaction between DBP and DARC by targeting the parasite ligand, while strategies targeting the receptor, DARC, have not been intensively investigated. The rapid increase in drug resistance and the lack of new effective drugs or a vaccine for malaria constitute a major threat and a need for novel therapeutics to combat disease. This review explores strategies that can be used to target the receptor. Inhibitors of DARC, which block DBP–DARC interaction, can potentially provide an effective strategy for preventing malaria caused by P. vivax.

Keywords: Plasmodium, vivax, knowlesi, DARC, malaria, treatment
 

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