Immunity
Volume 34, Issue 5, 27 May 2011, Pages 769-780
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Article
The Nod2 Sensor Promotes Intestinal Pathogen Eradication via the Chemokine CCL2-Dependent Recruitment of Inflammatory Monocytes

https://doi.org/10.1016/j.immuni.2011.04.013Get rights and content
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Summary

The intracellular sensor Nod2 is activated in response to bacteria, and the impairment of this response is linked to Crohn's disease. However, the function of Nod2 in host defense remains poorly understood. We found that Nod2−/− mice exhibited impaired intestinal clearance of Citrobacter rodentium, an enteric bacterium that models human infection by pathogenic Escherichia coli. The increased bacterial burden was preceded by reduced CCL2 chemokine production, inflammatory monocyte recruitment, and Th1 cell responses in the intestine. Colonic stromal cells, but not epithelial cells or resident CD11b+ phagocytic cells, produced CCL2 in response to C. rodentium in a Nod2-dependent manner. Unlike resident phagocytic cells, inflammatory monocytes produced IL-12, a cytokine that induces adaptive immunity required for pathogen clearance. Adoptive transfer of Ly6Chi monocytes restored the clearance of the pathogen in infected Ccr2−/− mice. Thus, Nod2 mediates CCL2-CCR2-dependent recruitment of inflammatory monocytes, which is important in promoting bacterial eradication in the intestine.

Highlights

► Nod2−/− mice exhibit impaired C. rodentium clearance and CCL2 production ► Reduced CCL2 was associated with impaired Gr1+ monocyte influx to the colon ► Intestinal stromal cells were the main producers of CCL2 ► Adoptive transfer of monocytes restored the clearance of C. rodentium in Ccr2−/− mice

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