Plasticity of monocyte development and monocyte fates

Monocytes are circulating myeloid immune precursor cells that are generated in the bone marrow. Mature monocytes are released into the circulation and, in case of need, recruited to peripheral sites of inflammation to differentiate into monocyte-derived effector cells. In absence of overt inflammation, monocytes also extravasate into selected tissues, where they complement tissue-resident macrophage compartments. Adjustment of these homeostatic monocyte infiltrates to local environment is critical to maintain health, as best established for the intestine. Defined gene expression changes that differ between gut segments presumably help strike the fine balance between the crucial function of these monocyte-derived macrophages as tissue rheostats and their detrimental hyperactivation. Environmental factors that dictate local monocyte differentiation remain incompletely understood. Definition of the latter could aid our general understanding of in vivo monocyte functions and their relation to inflammatory disorders. In this review, we summarize recent advances in our understanding of monocyte subsets, their differentiation into tissue macrophages, and selected contributions of monocyte-derived cells to steady-state physiology. Moreover, we will discuss emerging evidence for an intriguing bifurcation of monocyte development in the bone marrow and potential functional implications. Emphasis will be given to points of controversies, but we will largely focus on the healthy organism. For a discussion of monocyte and macrophage contributions to inflammatory conditions, we refer the reader to other dedicated reviews.