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Murine Monocytes: Origins, Subsets, Fates, and Functions

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  • Authors: Alexander Mildner1, Goran Marinkovic2, Steffen Jung3
  • Editor: Siamon Gordon4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel; 2: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel; 3: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel; 4: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0033-2016
  • Received 01 May 2016 Accepted 16 June 2016 Published 09 September 2016
  • Steffen Jung, s.jung@weizmann.ac.il
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  • Abstract:

    Monocytes are short-lived mononuclear phagocytes that circulate in the bloodstream and comprise two main subpopulations that in the mouse are best defined by the Ly6C marker. Intravascular functions of “classical” Ly6C monocytes and their interactions with other lymphoid and myeloid leukocytes in the circulation remain poorly understood. Rather, these cells are known to efficiently extravasate into tissues. Indeed, Ly6C monocytes and their descendants have emerged as a third, highly plastic and dynamic cellular system that complements the two classical, tissue-resident mononuclear phagocyte compartments, i.e., macrophages and dendritic cells, on demand. Following recruitment to injured tissue, Ly6C monocytes respond to local cues and can critically contribute to the initiation and resolution of inflammatory reactions. The second main murine monocyte subset, Ly6C cells, derive in steady state from Ly6C monocytes and remain in the vasculature, where the cells act as scavengers. Moreover, a major fraction of Ly6C monocytes adheres to the capillary endothelium and patrols the vessel wall for surveillance. Given the central role of monocytes in homeostasis and pathology, in-depth study of this cellular compartment can be highly informative on the health state of the organism and provides an attractive target for therapeutic intervention.

  • Citation: Mildner A, Marinkovic G, Jung S. 2016. Murine Monocytes: Origins, Subsets, Fates, and Functions. Microbiol Spectrum 4(5):MCHD-0033-2016. doi:10.1128/microbiolspec.MCHD-0033-2016.

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/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0033-2016
2016-09-09
2017-12-15

Abstract:

Monocytes are short-lived mononuclear phagocytes that circulate in the bloodstream and comprise two main subpopulations that in the mouse are best defined by the Ly6C marker. Intravascular functions of “classical” Ly6C monocytes and their interactions with other lymphoid and myeloid leukocytes in the circulation remain poorly understood. Rather, these cells are known to efficiently extravasate into tissues. Indeed, Ly6C monocytes and their descendants have emerged as a third, highly plastic and dynamic cellular system that complements the two classical, tissue-resident mononuclear phagocyte compartments, i.e., macrophages and dendritic cells, on demand. Following recruitment to injured tissue, Ly6C monocytes respond to local cues and can critically contribute to the initiation and resolution of inflammatory reactions. The second main murine monocyte subset, Ly6C cells, derive in steady state from Ly6C monocytes and remain in the vasculature, where the cells act as scavengers. Moreover, a major fraction of Ly6C monocytes adheres to the capillary endothelium and patrols the vessel wall for surveillance. Given the central role of monocytes in homeostasis and pathology, in-depth study of this cellular compartment can be highly informative on the health state of the organism and provides an attractive target for therapeutic intervention.

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Image of FIGURE 1
FIGURE 1

Schematic of murine monocyte development and monocyte fates. Ly6C monocytes are continuously generated in the adult BM in steady state from hematopoietic stem cells (HSCs) via a sequence comprising common myeloid precursors (CMPs), GMPs, MDPs ( 11 ), and cMoPs ( 14 ). The BM also harbors a rare population of Ly6C monocytes that could derive from Ly6C monocytes or cMoPs, but the function of this subset is unknown. Ly6C monocytes egress to the circulation, a process that requires CCR2 ( 18 ). Ly6C blood monocytes have a half-life of 20 h and several potential fates: (i) differentiation into Ly6C monocytes that patrol the endothelial surface of the vasculature; (ii) extravasation to selected tissues whose steady-state macrophage compartment requires maintenance by monocyte recruitment, such as the intestine ( 6 , 7 ); and (iii) recruitment to sites of tissue injury, infection, wounds, tumors, and inflammation, where the cells differentiate depending on local cues and give rise to cells with macrophage or DC features. Ly6C monocytes can also return from the circulation to the BM cavities ( 12 ), where their fate remains unclear. Of note, the scheme refers to monocyte development in steady state, while under challenge alternative developmental routes could be activated that might, for instance, bypass the MDP stage.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0033-2016
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Image of FIGURE 2
FIGURE 2

Example flow cytometric analysis of BM-resident monocyte precursors and blood monocytes. (A) Analysis of myeloid BM compartment of C57BL/6 and CX3CR1 C57BL/6 mouse ( 9 ). Blood cells were lysed with BD lysis buffer (#349202). Cells are gated for scatter, singlets, and Lin (Ter-119, B220, Ly6G, NK1.1, TCRγδ, CD4, CD8)-negative cells expressing CD115. This gate comprises CD135CD117 MDPs and CD135CD117 cMoPs and CD135CD117 monocytes. MDPs are CD11bLy6C, while cMoPs are CD11bLy6C. BM monocytes are CD11b and can be subdivided according to Ly6C expression into major Ly6C and minor Ly6C populations. Histogram shows CX3CR1-GFP reporter gene expression of MDPs, cMoPs, and monocytes, as compared to wild-type (WT) BM (gray). Note upregulation of reporter in Ly6C BM monocytes. (B) Analysis of blood monocyte compartment of C57BL/6 and CX3CR1 C57BL/6 mouse ( 9 ). Blood cells were lysed with BD lysis buffer (#349202). Cells are gated for scatter (excluding sideward scatted [SSC] high neutrophils), singlets, and lineage negative according to Lin marker expression (B220, CD19, CD3, CD4, CD8, Ly6G, NK1.1, TCRγδ). Lin cells comprise largely CD115CD11b monocytes. “Ly6C monocytes” (red) can be defined as Ly6CCD11cCCR2CD62LCX3CR1 and “Ly6C monocytes” (green) can be defined as Ly6CCD11cCCR2CD62LCX3CR1 cells. Note that “Ly6C monocytes” (blue) also show intermediate expression of the other markers, as seen in the respective histograms. This supports the notion that these cells are a transitional population. FSC, forward scatter.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0033-2016
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