How cell migration helps immune sentinels

Abstract

The immune system relies on the migratory capacity of its cellular components, which must be mobile in order to defend the host from invading micro-organisms or malignant cells. This applies in particular to immune sentinels from the myeloid lineage, i.e. macrophages and dendritic cells. Cell migration is already at work during mammalian early development, when myeloid cell precursors migrate from the yolk sac, an extra embryonic structure, to colonize tissues and form the pool of tissue-resident macrophages. Later, this is accompanied by a migration wave of precursors and monocytes from the bone marrow to secondary lymphoid organs and the peripheral tissues. They differentiate into DCs and monocyte-derived macrophages. During adult life, cell migration endows immune cells with the ability to patrol their environment as well as to circulate between peripheral tissues and lymphoid organs. Hence migration of immune cells is key to building an efficient defense system for an organism. In this review, we will describe how cell migratory capacity regulates the various stages in the life of myeloid cells from development to tissue patrolling, and migration to lymph nodes. We will focus on the role of the actin cytoskeletal machinery and its regulators, and how it contributes to the establishment and function of the immune system.

Keywords: actin; ameboid motility; cell migration; cytoskeleton; dendritic cell; myeloid cells; tissue-resident macrophage.

FIGURE 1

Myeloid cell compartment establishment. Is achieved during the three consecutive waves of hematopoiesis that lead to the establishment of the hematopoietic system. Myeloid progenitors develop from the Yolk sac and originate macrophage progenitors that later differentiate into microglia in the brain, that transit from a ramified state to an ameboid phenotype when activated. The second wave also occurs in the Yolk sac and it is characterized by the development of multipotent erythro-myeloid progenitors, which give rise to tissue-resident macrophages: Langerhans cells in the skin, alveolar macrophages in the lung and Kupffer cells in the liver. A third proposed wave in which multipotent progenitors emerge in both the Yolk sac and intra-embryonic tissues, including the para-aortic splanchnopleura (P-Sp) and aorta- gonad-mesonephros (AGM), give rise to long term-HSCs that migrate and colonize the fetal liver (FL), and represent a long-lived pool that will last throughout adulthood. These long term-HSCs are capable to self-renew and long-term repopulate all hematopoietic lineages during adulthood, and give rise to dendritic cells, that are present in all tissues.