Cell Reports
Volume 20, Issue 8, 22 August 2017, Pages 1830-1843
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Article
Triggering of NOD2 Receptor Converts Inflammatory Ly6Chigh into Ly6Clow Monocytes with Patrolling Properties

https://doi.org/10.1016/j.celrep.2017.08.009Get rights and content
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Highlights

  • Triggering NOD2 converts Ly6Chigh into Ly6Clow patrolling monocytes

  • Converted Ly6Chigh monocytes express typical markers of patrolling monocytes

  • Triggering NOD2 increases crawling of converted Ly6Chigh monocytes

  • Triggering NOD2 converts human primary CD142+ CD16 into CD14± CD162+ monocytes.

Summary

The signals that regulate the fate of circulating monocytes remain unknown. In the present study, we demonstrate that triggering of the NOD2 receptor by muramyl dipeptide (MDP) converts inflammatory Ly6Chigh monocytes into patrolling Ly6Clow monocytes. Administration of MDP to Nr4a1−/− mice, which lack Ly6Clow monocytes, or to Ly6Clow-depleted mice led to the emergence of blood-patrolling monocytes with a profile similar to that of Ly6Clow monocytes, including high expression of CX3CR1 and LFA1. Using intravital microscopy in animal models of inflammatory diseases, we also found that converted Ly6Chigh monocytes patrol the endothelium of blood vessels and that their presence contributes to a reduction in the inflammatory response following MDP injection. Our results demonstrate that NOD2 contributes to the regulation of blood monocytes and suggest that it could be therapeutically targeted to treat inflammatory diseases.

Keywords

inflammatory monocytes
patrolling monocytes
NOD2 receptor
monocyte polarization
inflammation
NOD2 agonists
innate response

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These authors contributed equally

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