Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

Abstract

Circulating monocytes (Mos) may continuously repopulate macrophage (MAC) or dendritic cell (DC) populations to maintain homeostasis. MACs and DCs are specialized cells that play different and complementary immunological functions. Accordingly, they present distinct migratory properties. Specifically, whereas MACs largely remain in tissues, DCs are capable of migrating from peripheral tissues to lymphoid organs. The aim of this work was to analyze the expression of the fractalkine receptor (CX 3 CR1) during the monocytic differentiation process. Freshly isolated Mos express high levels of both CX 3 CR1 mRNA and protein. During the Mo differentiation process, CX 3 CR1 is downregulated in both DCs and MACs. However, MACs showed significantly higher CX 3 CR1 expression levels than did DC. We also observed an antagonistic CX 3 CR1 regulation by interferon (IFN)-c and interleukin (IL)-4 during MAC activation through the classical and alternative MAC pathways, respectively. IFN-c inhibited the loss of CX 3 CR1, but IL-4 induced it. Additionally, we demonstrated an association between CX 3 CR1 expression and apoptosis prevention by soluble fractalkine (sCX 3 CL1) in Mos, DCs and MACs. This is the first report demonstrating sequential and differential CX 3 CR1 modulation during Mo differentiation. Most importantly, we demonstrated a functional link between CX 3 CR1 expression and cell survival in the presence of sCX 3 CL1.

Metastatic breast cancer cells induce altered microglial morphology and electrical excitability in vivo

“…As CX3CR1 is also expressed on peripheral blood monocytes, natural killer cells and dendritic cells in addition to microglia [38,47], it is possible that some of the accumulation of GFP-positive cells that we observed at the lesion site may be due to recruitment of other CX3CR1-expressing immune cells. However, the TMEM119 staining argues against this and suggests that there was minimal infiltration of other immune cell types.…”

“…3a-c, arrows). In addition to microglia, CX3CR1 is also expressed on macrophages, certain subtypes of T cells and natural killer cells [38,47,48], raising the possibility that some of the GFP-positive population at the lesion site may constitute other cell types. The microglia-specific marker TMEM119 [49] was expressed on ramified microglia in control brain parenchyma and there was also strong staining at the lesion site ( Fig.…”

Cellular and molecular regulation of innate inflammatory responses

“…Ligation of TLRs by microbial products in DCs rapidly induces the expression of inflammatory cytokines, chemokines and chemokine receptors, co-stimulatory molecules and MHC molecules, allowing procession and presentation of antigens to T cells, and therefore play essential roles in determining the activation and differentiation of T-cell subsets. [122][123][124][125][126][127] The activation of DCs by TLR agonists is accompanied by a rapid increase in glycolysis DC which is dependent on signaling via the kinases TBK1, IKKε and Akt. TLR-driven glycolytic flux serves an essential role in supporting the de novo synthesis of fatty acids for activation and function of DCs.…”

Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS

“…Although both resident microglia and peripherally derived monocytes express the CX3CR1 [29, 30], only the latter express CCR2, providing a powerful marker to discriminate between resident microglia and infiltrating monocyte in the brain. CX3CR1 + microglia are widely distributed through the brain parenchyma, while CCR2 + monocytes are rarely seen in the healthy brain [29].…”