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Nat Immunol. 2016 Nov;17(11):1263-1272. doi: 10.1038/ni.3564. Epub 2016 Sep 26.

CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.

Author information

1
Toronto General Research Institute, University Health Network, Toronto, Canada.
2
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
3
Krembil Research Institute, University Health Network, Toronto, Canada.
4
Department of Immunology, University of Toronto, Toronto, Canada.
5
Center for Immunity and Infection Lausanne, Department of Biochemistry, University of Lausanne, Switzerland.
6
Department of Medicine, University of Toronto, Toronto, Canada.

Abstract

Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse transendothelial migration (RTM) into the arterial circulation after systemic stimulation of pattern-recognition receptors (PRRs). This process was dependent on expression of the chemokine receptor CCR7 and its ligand CCL19 by intimal myeloid cells. In mice infected with the intracellular pathogen Chlamydia muridarum, blood monocytes disseminated infection to the intima. Subsequent CCL19-CCR7-dependent RTM was critical for the clearance of intimal C. muridarum. This process was inhibited by hypercholesterolemia. Thus, RTM protects the normal arterial intima, and compromised RTM during atherogenesis might contribute to the intracellular retention of pathogens in atherosclerotic lesions.

PMID:
27668800
DOI:
10.1038/ni.3564
[Indexed for MEDLINE]

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