Capturing the Fantastic Voyage of Monocytes Through Time and Space

Abstract

Monocytes are a subset of cells that are categorized together with dendritic cells (DCs) and macrophages in the mononuclear phagocyte system (MPS). Despite sharing several phenotypic and functional characteristics with MPS cells, monocytes are unique cells with the ability to function as both precursor and effector cells in their own right. Before the development of hematopoietic stem cells (HSCs) in utero , monocytes are derived from erythro-myeloid precursors (EMPs) in the fetal liver that are important for populating the majority of tissue resident macrophages. After birth, monocytes arise from bone marrow (BM)-derived HSCs and are released into the circulation upon their maturation, where they survey peripheral tissues and maintain endothelial integrity. Upon sensing of microbial breaches or inflammatory stimuli, monocytes migrate into tissues where their plasticity allows them to differentiate into cells that resemble macrophages or DCs according to the environmental niche. Alternatively, they may also migrate into tissues in the absence of inflammation and remain in an undifferentiated state where they perform homeostatic roles. As monocytes are typically on the move, the availability of intravital imaging approaches has provided further insights into their trafficking patterns in distinct tissue compartments. In this review, we outline the importance of understanding their functional behavior in the context of tissue compartments, and how these studies may contribute towards improved vaccine and future therapeutic strategies.

Biological Considerations in Scaling Up Therapeutic Cell Manufacturing

“…Monocytes and macrophages form the mononuclear phagocyte system and are essential components of inflammation and tissue repair (Jung, 2018). Blood monocytes that enter inflamed sites in the body respond to local inflammatory stimuli and differentiate into monocyte-derived cells that resemble macrophages or DCs (Teh et al, 2019). At early stages of inflammation, tissue-infiltrating monocytes secrete pro-inflammatory TNF-a and IL-1, while monocytes found at later stages of inflammation exhibit anti-inflammatory properties (Teh et al, 2019).…”

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

“…Monocytes are large mononuclear cells of the innate immune system and often described as highly plastic cells with the ability to function as both precursor and effector cells [92]. Monocytes constitute approximately 5-10% of peripheral blood leukocytes in healthy humans [93].…”

Monocyte recruitment to the inflamed central nervous system: migration pathways and distinct functional polarization

“…Tissue inflammation drives the mobilization of monocytes from the bone marrow and from splenic secondary reservoir into the bloodstream 15,51 , from which these cells can potentially access the CNS at the level of the BBB, the BCSFB, or at the subarachnoid vasculature within the leptomeninges 6 indicating that neuroinflammatory conditions can increase the extravasation of monocytederived cells as shown for other immune cells 44,52,53 . While in vitro inflammatory conditions decreased pMBMEC TEER implying impaired junctional barrier properties, immune staining did not reveal any significant changes in junctional continuity, in line with the notion that BBB physical disruption is not strictly needed for cell extravasation 54 .…”

“…Within CNS lesions in both MS and EAE, monocyte-derived macrophages are the most represented infiltrating immune cells 13,14 . In the mouse system, these players arise from inflammatory and patrolling circulating monocytes, respectively characterized by high and low expression of the differentiation marker Ly6C 15 . These distinct cell types display differential expression of the chemokine receptors CCR2 and CX3CR1 16 , with Ly6C low CX3CR1 high patrolling cells required to maintain endothelial homeostasis, and inflammatory Ly6C high CX3CR1 low monocytes showing fast CCR2-mediated recruitment to inflamed tissues 17,18 .…”