All non-classical monocytes in this study exhibited less CD36, CD64, CCR2, CD11b, and CD33, but more CD45, CD11c, and HLA-DR expression than classical and intermediate monocytes, becoming consistent in terms of useful surface marker selection for reliable monocyte subset isolation (20)

All non-classical monocytes in this study exhibited less CD36, CD64, CCR2, CD11b, and CD33, but more CD45, CD11c, and HLA-DR expression than classical and intermediate monocytes, becoming consistent in terms of useful surface marker selection for reliable monocyte subset isolation (20). be clustered in smaller, transcriptionally unique subsets (17). Using a mass cytometry approach, Thomas and colleagues showed that traditional gating on CD14 and CD16 frequently led to contaminations of intermediate and non-classical monocytes; instead, the addition of markers, such as CD36, CCR2, HLA-DR, and CD11c enabled more precise separation of human monocytes (19). Another mass cytometry protocol increased the resolution of the non-classical monocyte phenotype and distinguished CD14dimCD16+SLAN? from CD14dimCD16+SLAN+ non-classical monocytes. All non-classical monocytes in this study exhibited less CD36, CD64, CCR2, CD11b, and CD33, but more CD45, CD11c, and HLA-DR expression ML277 than classical and intermediate monocytes, becoming consistent in terms of useful surface marker selection for reliable monocyte subset isolation (20). Lastly, another study counted 8 monocyte clusters in ML277 healthy individuals using a broad range of lineage, adhesion, antigen presentation, migration, activation, cell death, and survival markers. Classical monocyte subsets differed around the levels of IgE, CD61/CD9, and CD93/CD11a, whilst non-classical monocyte subsets were further divided by the expression of CD9 and SLAN which linked them to increased efferocytosis and migration to CCL16 in comparison with SLAN? non-classical monocytes (21). It will be interesting to learn in larger cohorts of healthy and diseased individuals whether such cellular subsets are of functional relevance and and secretion of pro-inflammatory cytokines, such as IL-1 and TNF in response to LPS or ssRNA activation ML277 (54). Moreover, all circulating monocytes in obese donors express more CX3CR1, implying an increased chemotactic potential toward CX3CL1-secreting adipocytes (54). In accordance with this observation, obesity has been characterized by an increased amount of monocyte-derived adipose tissue macrophages in both mouse and human (53, 56). Caloric PMCH restriction has beneficial effects in many chronic metabolic disorders like T2D, non-alcoholic liver disease and CVD (57C59) and short-term fasting is sufficient to reduce the numbers of all monocyte populations in healthy human subjects (60). Nevertheless, in depth characterization of mechanistic changes occurring due to different dietary habits is still lacking. Modern high-dimensional technologies (e.g., multi-color circulation cytometry, mass cytometry, single-cell RNA-seq) will contribute to understanding main and secondary effects of diet around the monocyte compartment, possibly dissecting the influence of single macronutrients. Human Monocyte Differentiation in the Gut is usually Influenced by Dietary Components Metabolites play a major role in the differentiation of monocytes and impact their functionalities, as exemplified by the short chain fatty acid -hydroxybutyrate, which upon its release from the liver under prolonged fasting, has been shown to suppress the NLRP3 inflammasome-induced IL-1 and IL-18 production by human monocytes (61). Similarly, Goudot and colleagues found that activation of human monocytes with 6-formylin-dolo(3,2-b)carbazole (FICZ), an endogenous ligand for the environmental sensor aryl hydrocarbon receptor (62), biases monocyte differentiation into moDCs via a BLIMP-1-dependent mechanism (63). Finally, bacterial butyrate imprints a host protection program via epigenetic remodeling during monocyte to macrophage differentiation in the lamina propria (64). In more detail, in the absence of tissue-damaging inflammation, butyrate induces macrophages to upregulate antimicrobial proteins, such as calprotectin. The mechanisms by which metabolites alter monocyte functions have many aspects in common with the concept of innate immune cell memory where initial priming with a stimulus prospects to sustained epigenetic reprogramming that culminates in a phenotypic switch upon subsequent challenge (42, 65). Emerging evidence on diet-associated triggers shows that they can induce.