Abstract
Low-density granulocytes (LDGs) have been characterized as important immune cells during healthy and disease states in humans, including microbial infections, cancer, and autoimmune dysfunction. However, the classification of this cell type is similar to other immune cells (e.g., neutrophils, myeloid-derived suppressor cells) and ambiguous functional standards have rendered LDG identification and isolation daunting. Furthermore, most research involving LDGs has mainly focused on adult cells and subjects, leaving increased uncertainty surrounding younger populations, especially in vulnerable neonatal groups where LDG numbers are elevated. This review aims to bring together the current research in the field of LDG biology in the context of immunity to disease, with a focus on infection. In addition, we propose to highlight the gaps in the field that, if filled, could improve upon isolation techniques and functional characterizations for LDGs separate from neutrophils and myeloid-derived suppressor cells (MDSCs). This will not only enhance understanding of LDGs during disease processes and how they differ from other cell types but will also aid in the interpretation of comparative studies and results with the potential to inform development of novel therapeutics to improve disease states in patients.
Highlights
Many studies working with Low-density granulocytes (LDGs) within these disease states classify LDGs as granulocytic myeloid-derived suppressor cells and low-density neutrophils (LDNs), with similar cell surface marker expression and functional characterizations utilized for each cell type
LDGs as granulocytic myeloid-derived suppressor cells (gMDSCs), which seems to be a general consensus among the cancer field, save for a few studies using the nomenclature LDN (Table 1). This reasserts the question in the cancer field, are all gMDSCs from cancer patients equivalent to LDGs, or is there sufficient heterogeneity that both populations with differential phenotypic and functional characteristics exist? We suggest a need for single cell sequencing-based studies that are paired with functional assays using low-density cell granulocyte fractions from cancer patients to better discern the differences between gMDSCs and LDGs in this field
LDGs really LDGs or could they be another associated cell type? If these cells are LDGs, how do we adjust our thinking on what we call gMDSCs, LDNs, and LDGs during infections and cancer?. It is clear from this brief review that there are questions that still must be addressed in regard to the classification of LDGs throughout disciplines
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Many studies working with LDGs within these disease states classify LDGs as granulocytic myeloid-derived suppressor cells (gMDSCs) and low-density neutrophils (LDNs), with similar cell surface marker expression and functional characterizations utilized for each cell type. In addition to the classification and functional challenges, LDG research has mainly focused on adult cells and subjects This has left increased uncertainty in fields surrounding younger populations, especially in vulnerable neonatal groups where LDG/gMDSC numbers are elevated even without disease [8]. We highlight discrepancies in the field that, if improved upon, could enhance isolation and functional characterizations for LDGs independent of neutrophils and myeloid-derived suppressor cells (MDSCs) These improvements will clarify the importance of each cell type during disease states, aid in the comparison of published studies, and in the end could lead to improved therapeutic development and human health
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