Figure 2. Monocyte heterogeneity.

Monocytes originate in the bone marrow from a common haematopoietic stem cell (HSC). They undergo differentiation steps during which they commit to the myeloid and then to a monocyte lineage. In response to macrophage colony-stimulating factor, they divide and differentiate into monoblasts and then pro-monocytes before becoming monocytes, which exit the bone marrow and enter the bloodstream. In mice, there is evidence of two distinct monocyte populations in the blood that have different phenotypes and biochemical signatures. GR1⁺CX₃CR1^low (CX₃C-chemokine receptor 1) monocytes rapidly exit the blood, and for this reason they are referred to as ‘inflammatory’ monocytes. GR1⁻ monocytes have been termed ‘resident’ monocytes to differentiate them from the other population. It remains unknown whether inflammatory monocytes mature into resident monocytes in the blood or whether these two cells represent distinct monocyte populations. Human monocytes can also be divided into two populations, but the designations inflammatory and resident do not apply to these populations. Monocytes migrate to different tissues, where they replenish tissue-specific macrophages. CNS, central nervous system; GM-CFU, granulocyte/macrophage colony-forming unit; M-CFU, macrophage colony-forming unit.