Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2

Abstract

Monocytes recruited to tissues mediate defense against microbes or contribute to inflammatory diseases. Regulation of the number of circulating monocytes thus has implications for disease pathogenesis. However, the mechanisms controlling monocyte emigration from the bone marrow niche where they are generated remain undefined. We demonstrate here that the chemokine receptor CCR2 was required for emigration of Ly6Chi monocytes from bone marrow. Ccr2−/− mice had fewer circulating Ly6Chi monocytes and, after infection with Listeria monocytogenes, accumulated activated monocytes in bone marrow. In blood, Ccr2−/− monocytes could traffic to sites of infection, demonstrating that CCR2 is not required for migration from the circulation into tissues. Thus, CCR2-mediated signals in bone marrow determine the frequency of Ly6Chi monocytes in the circulation.

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Figure 1: Ly6C+ monocyte frequencies are diminished in the bloodstream and increased in the bone marrow of Ccr2−/− mice.
Figure 2: Ly6Chi monocytes differentiate into TipDCs.
Figure 3: Ly6C+ TNF-producing monocytes accumulate in the bone marrow of Ccr2−/− mice infected with L. monocytogenes.
Figure 4: Characterization of retained monocytes in the bone marrow of infected Ccr2−/− mice.
Figure 5: CCR2 is dispensable for monocyte migration from the bloodstream to infected tissues.
Figure 6: Ccr2−/− monocytes migrate to the sites of bacterial replication in the white pulp.

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Acknowledgements

Supported by the National Institutes for Health (E.G.P.).

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Correspondence to Natalya V Serbina.

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Supplementary information

Supplementary Fig. 1

Retained monocytes in bone marrow of infected Ccr2−/− mice express myeloid marker 7/4. (PDF 31 kb)

Supplementary Fig. 2

Ccr2−/− monocyte migration from the bloodstream to infected spleen. (PDF 57 kb)

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Serbina, N., Pamer, E. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7, 311–317 (2006). https://doi.org/10.1038/ni1309

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