Abstract
Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as “assistants” in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several ‘checkpoints’ from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS) diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets.
Highlights
Diseases of the central nervous system (CNS) are some of the most devastating contributors to disease burden worldwide, and are associated with significant costs to healthcare and productivity [1,2,3]
This indicates that, under certain circumstances, leukocytes may be invited guests to the CNS—participants in a coordinated series of interactions with the brain’s endothelial, glial, and epithelial barriers to contribute to brain homeostasis
Spotlight on Coordinated Chemotaxis: The CCL2/CCR2 Pathway. This concept of “invited” migration to the brain parenchyma during demyelination is even better demonstrated with new insights gained regarding chemokine ligand 2 (CCL2), a crucial chemokine for egress of monocytes from bone marrow, and their transport through both endothelial and glial checkpoints to the brain parenchyma
Summary
Diseases of the central nervous system (CNS) are some of the most devastating contributors to disease burden worldwide, and are associated with significant costs to healthcare and productivity [1,2,3]. Despite initial controversy as to their origin, it is established that microglia are derived from early yolk sac erythromyeloid precursors and migrate to the brain during early embryogenesis [14,15,16], where they remain exclusively throughout life without substantial contribution from bone marrow-derived cells, unless recruited in response to distress signals from the CNS parenchyma and associated endothelial and glial barriers [11,17,18] In their ramified state, microglia are far from ‘resting’, their processes continuously extend and retract to survey the surrounding parenchyma [19]. Other researchers have used bone marrow chimeras and promoter-driven transgenic animals to label resident and infiltrating cells separately, and have found that in many conditions, the two subsets of cells vary considerably in their ability to phagocytose pathological deposits of protein, recruit other immune cells via antigen presentation, and contribute to pathology via production of neurotoxic substances [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
