Phagocyte Development

Abstract

Mature circulating white blood cells can be divided into two lineages: lymphoid and myeloid. The lymphoid lineage consists of T, B, NK and innate lymphoid cells, while the myeloid lineage includes functionally and morphologically distinct cell types including mononuclear phagocytes (monocytes, dendritic cells and macrophages), granulocytes (neutrophils, basophils, mast cells and eosinophils) and platelets. Granulocytes and mononuclear phagocytes are key players at all stages of the immune response from its genesis to its resolution, and come under the banner of phagocytes. Damaged or infected tissue releases chemoattractants that rapidly recruit these phagocytes to the site of injury. Once at the inflamed site, these cells coordinate and carry out immune functions, playing a key role in host defence. The recent past has seen major progress in our understanding of phagocyte developmental biology. Here, we discuss the latest advances in myeloid development, underpinning our current understanding of how these cells are generated and maintained. Key Concepts The myeloid lineage includes functionally and morphologically distinct cell types including mononuclear phagocytes (monocytes, dendritic cells and macrophages) and granulocytes (neutrophils, basophils, mast cells and eosinophils). The majority of tissue resident macrophages are generated before birth and are long‐lived self‐maintained cells throughout adulthood. Dendritic cells prime naïve T cells and are derived from a common precursor in the bone marrow that gives rise exclusively to this family of cells. Monocytes are the principal circulating mononuclear phagocyte. Monocytes develop in the bone marrow from a common monocyte progenitor, once in the circulation classical monocytes have the potential to convert into nonclassical monocytes. Classical monocytes are known to repopulate resident mononuclear phagocyte populations and have potent effector functions during immunity. Granulocyte subsets have a complex morphology with a segmented nucleus and each subset contains granules endowing them with a specific role in host defence. Transcription and growth factors control and dictate the development of phagocytes.

Developmental and Functional Heterogeneity of Monocytes

“…While CD209a + MHCII + Ly6C Hi-to-int monocytes are proposed to give rise to monocyte-derived DC under pathological conditions (Menezes et al, 2016), the origin of these cells is currently uncertain, even though these cells likely develop independently of C/EBPb (Mildner et al, 2017). Human CD14 + CD16 + monocytes likewise show heterogeneity (Villani et al, 2017) and are characterized in general by higher HLA gene family expression (Gren et al, 2015;Patel and Yona, 2018;Patel et al, 2017;Schmidl et al, 2014;Zawada et al, 2011). For certain newly identified monocyte subsets we are still searching for the homologous equivalent in mice and men.…”

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

“…Nevertheless, monocyte-derived cells can replace the embryonic counterparts depending on the tissue concerned. For further reading on the ontogeny, heterogeneity, and specific functions of monocytes we refer the reader to a few recent publications [1350,1352,[1355][1356][1357][1358][1359].…”