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Updated: Jul 29, 2025
Characterization of Human Monocyte Subsets by Whole Blood Flow Cytometry Analysis
Published on: October 17, 2018
Monocyte Differentiation and Heterogeneity: Inter-Subset and Interindividual Differences
Helen Williams1,2, Corinne Mack1,2, Rana Baraz1,2
1Vascular Biology Research Centre, Department of Surgery, Westmead Hospital, Westmead, NSW 2145, Australia.
Insights
Human monocyte subsets (classical, intermediate, nonclassical) display complex heterogeneity. This variation exists within subsets, across health and disease states, and between individuals, impacting research and clinical relevance.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human monocytes comprise three main subsets: classical, intermediate, and nonclassical.
- These subsets are distinguished by CD14 and CD16 expression and exhibit distinct phenotypes and functions.
- Existing research acknowledges functional differences between these monocyte subsets.
Purpose of the Study:
- To explore the multi-dimensional heterogeneity of human monocyte subsets.
- To discuss the implications of intra-subset variation for monocyte classification and function.
- To highlight the relevance of monocyte heterogeneity in health and disease.
Main Methods:
- Phenotypic analysis of monocyte subsets using markers like CD14 and CD16.
- Comparative studies of monocyte function in steady-state and disease conditions.
- Investigation of interindividual variability in monocyte populations.
Main Results:
- Monocyte heterogeneity is multi-dimensional, extending beyond distinct subset differences.
- Significant heterogeneity is observed within each monocyte subset.
- Interindividual differences in monocyte subsets exist even in healthy individuals, potentially influenced by microenvironmental factors.
Conclusions:
- Understanding monocyte heterogeneity is crucial for accurate classification and functional assignment.
- Intra-subset and interindividual variations significantly impact the study of monocytes in health and disease.
- Microenvironmental influences may lead to long-lasting changes in monocyte precursors and their derived cells.
Abstract:
The three subsets of human monocytes, classical, intermediate, and nonclassical, show phenotypic heterogeneity, particularly in their expression of CD14 and CD16. This has enabled researchers to delve into the functions of each subset in the steady state as well as in disease. Studies have revealed that monocyte heterogeneity is multi-dimensional. In addition, that their phenotype and function differ between subsets is well established. However, it is becoming evident that heterogeneity also exists within each subset, between health and disease (current or past) states, and even between individuals. This realisation casts long shadows, impacting how we identify and classify the subsets, the functions we assign to them, and how they are examined for alterations in disease. Perhaps the most fascinating is evidence that, even in relative health, interindividual differences in monocyte subsets exist. It is proposed that the individual's microenvironment could cause long-lasting or irreversible changes to monocyte precursors that echo to monocytes and through to their derived macrophages. Here, we will discuss the types of heterogeneity recognised in monocytes, the implications of these for monocyte research, and most importantly, the relevance of this heterogeneity for health and disease.
