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Monocyte recruitment during infection and inflammation

Nature Reviews Immunology volume 11, pages 762–774 (2011)Cite this article

Subjects

Key Points

  • Monocytes are a heterogeneous population of myeloid cells that originate from progenitors in the bone marrow and traffic via the bloodstream to peripheral tissues.

  • Monocyte recruitment is guided by chemokines that bind to receptors expressed on the monocyte cell surface. The process is believed to follow a general paradigm of leukocyte adhesion and trafficking, and thus depends on the interactions of various adhesion molecules.

  • Circulating monocytes traffic into tissues during both homeostasis and inflammation. When conditioned by local growth factors, pro-inflammatory cytokines and microbial products, monocytes can differentiate into macrophage or dendritic cell populations.

  • The recruitment of monocytes is essential for effective control and clearance of bacterial, protozoal, fungal and viral infections, but recruited monocytes can also be deleterious and cause immunopathology during certain infections.

  • Monocyte recruitment contributes to the pathogenesis of aseptic inflammatory diseases. Different subsets of monocytes are recruited to the aorta during atherosclerosis and possibly have distinct roles at this site.

  • Monocyte egress from the bone marrow depends on CC-chemokine receptor 2 (CCR2), a chemokine receptor that binds to CC-chemokine ligand 2 (CCL2) and CCL7. Sensitive detection of circulating microbial molecules or pro-inflammatory cytokines by bone marrow-resident cells (such as mesenchymal stem cells and CXCL12-abundant reticular cells), with commensurate induction of CCL2, provides a mechanism to modulate the frequency of circulating inflammatory monocytes. This suggests that microorganisms may drive inflammatory disease in an otherwise 'sterile' tissue environment.

Abstract

Monocytes originate from progenitors in the bone marrow and traffic via the bloodstream to peripheral tissues. During both homeostasis and inflammation, circulating monocytes leave the bloodstream and migrate into tissues where, following conditioning by local growth factors, pro-inflammatory cytokines and microbial products, they differentiate into macrophage or dendritic cell populations. Recruitment of monocytes is essential for effective control and clearance of viral, bacterial, fungal and protozoal infections, but recruited monocytes also contribute to the pathogenesis of inflammatory and degenerative diseases. The mechanisms that control monocyte trafficking under homeostatic, infectious and inflammatory conditions are being unravelled and are the focus of this Review.

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Figure 1: Trafficking of circulating monocyte subsets.
Figure 2: Monocyte recruitment is crucial for defence against a broad range of pathogenic microorganisms.
Figure 3: Pro-inflammatory cytokines and TLR ligands promote the emigration of LY6Chi monocytes from the bone marrow.
Figure 4: Models of CCL2-mediated emigration of LY6Chi monocytes from the bone marrow.

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Acknowledgements

This work was supported by US National Institutes of Health grants 5R37AI039031 and 5P01CA023766-31 (to E.G.P.).

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  1. Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Chao Shi & Eric G. Pamer

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Glossary

Polyinosinic–polycytidylic acid

(polyI:C). A substance that is used as a mimic of viral double-stranded RNA.

CXCL12-abundant reticular cells

(CAR cells). A type of stromal cell found in the bone marrow that expresses high levels of CXC-chemokine ligand 12. CAR cells can function as adipo-osteogenic progenitors, which are required for the proliferation of haematopoietic stem cells (HSCs), B cells and erythroid progenitor cells, and for maintaining HSCs in an undifferentiated state.

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Shi, C., Pamer, E. Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11, 762–774 (2011). https://doi.org/10.1038/nri3070

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