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Chapter 9 : Murine Monocytes: Origins, Subsets, Fates, and Functions

Authors: Alexander Mildner1, Goran Marinkovic2, Steffen Jung3
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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
Content Type: Monograph
Publication Year: 2017

Category: Microbial Genetics and Molecular Biology

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Abstract:

Monocytes are a conserved population of leukocytes that are present in all vertebrates, with some evidence of a parallel cell population in fly hemolymph ( ). Monocytes are defined by their location in the bloodstream, their phenotype and nuclear morphology, as well as by their characteristic gene and microRNA expression signatures ( ). In mice, monocytes represent 4% of the nucleated cells in the blood, with considerable marginal pools in the spleen and lungs that can be mobilized on demand ( ). Within the blood, monocytes, and in particular the classical Ly6C mouse subset, exhibit a characteristically short half-life of 20 h ( ), akin to that of similar ephemer neutrophils ( ).

Citation: Mildner A, Marinkovic G, Jung S. 2017. Murine Monocytes: Origins, Subsets, Fates, and Functions, p 141-153. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0033-2016
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Murine Monocytes: Origins, Subsets, Fates, and Functions
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Citation: Mildner A, Marinkovic G, Jung S. 2017. Murine Monocytes: Origins, Subsets, Fates, and Functions, p 141-153. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0033-2016
/content/10.1128/9781555819194.chap9.fig9-1
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 ( ), and cMoPs ( ). 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 ( ). 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 ( ); 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 ( ), 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.

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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 ( ), and cMoPs ( ). 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 ( ). 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 ( ); 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 ( ), 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.

Citation: Mildner A, Marinkovic G, Jung S. 2017. Murine Monocytes: Origins, Subsets, Fates, and Functions, p 141-153. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0033-2016
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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 ( ). 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 ( ). 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.

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10.1128/9781555819194/fig9-2.gif
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 ( ). 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 ( ). 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.

Citation: Mildner A, Marinkovic G, Jung S. 2017. Murine Monocytes: Origins, Subsets, Fates, and Functions, p 141-153. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0033-2016
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