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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Roufaiel M,Gracey E,Siu A,Zhu SN,Lau A,Ibrahim H,Althagafi M,Tai K,Hyduk SJ,Cybulsky KO,Ensan S,Li A,Besla R,Becker HM,Xiao H,Luther SA,Inman RD,Robbins CS,Jongstra-Bilen J,Cybulsky MI

doi

10.1038/ni.3564

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

1263-1272

issue

11

eissn

1529-2908

issn

1529-2916

pii

ni.3564

journal_volume

17

pub_type

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