Abstract
Chemokine receptors such as C-C chemokine receptor 5 (CCR5) are activated through interaction with their ligands and are well known for their role in chemotaxis and signal transduction. While serving these roles, cellular responses are effected, hence the immune function of these molecules is established. Given the role of CCR5 in immune function and that the immune and metabolic systems are interlinked, subsequent immune-directed changes should be measurable at a metabolic level. Numerous investigations have reported on metabolic changes associated with CCR5 status in the presence of disease, so as to understand whether specific CCR5 genotypes, frequency and/or levels offer protection to the host or not. However, these metabolic changes were recorded using older conventional techniques. Depending on certain factors such as the disease model, the geography of the samples and/or the ethnic group under study, the role of CCR5 in disease differs. In addition, little is known about CCR5’s role in the absence of an enhanced inflammatory state, such as when infection persists. Metabolomics is defined as the study of metabolites and informs on metabolic changes within living organisms as induced by various stimuli, such as the interaction of CCR5 with its ligand. Since metabolomics reflects the underlying biochemical activity and state of cells/tissues, this review proposes it as a tool to clarify the contrasting roles of CCR5.
Highlights
Chemokines are small proteins with molecular weights ranging from 7 to 15 kilodalton [1]
The main focus was to review the role of chemokine receptor 5 (CCR5) in disease since genotype influences the expression and/or the amount of CCR5 present on the cell surface, susceptibility to infection and disease pathogenesis
CCR5 is crucial for mediating signal transduction and activating immune responses which impact the cell’s metabolism
Summary
Chemokines are small proteins with molecular weights ranging from 7 to 15 kilodalton (kDa) [1]. Given the role of CCR5 in immune function, subsequent changes linked to the chemokine receptor should be measurable at the metabolic level. It is reported that Jiankui used CRISPR-Cas to generate genetically modified embryos carrying the CCR5∆32 mutation This results in an individual with cells devoid of functional CCR5 on their surface [49]. Whilst this mutation is generally protective against HIV-1 infection, the long-term effects of such an experiment are not yet known. Considering the role of chemokines, it is anticipated that the differential expression patterns of chemokine receptors and their respective ligands may play a role in inflammation and impact the immune response and metabolism to influence disease progression and/or clinical outcome. Given CCR5’s immuno-metabolic effects, metabolomics is proposed as an approach with which to clarify the receptor’s role
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