CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.
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.
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Mark
http://orcid.org/0000-0003-4174-1043
M
Roufaiel
Krembil Research Institute, University Health Network, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Eric
E
Gracey
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Allan
A
Siu
Toronto General Research Institute, University Health Network, Toronto, Canada.
Su-Ning
SN
Zhu
Toronto General Research Institute, University Health Network, Toronto, Canada.
Andrew
A
Lau
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Hisham
H
Ibrahim
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Marwan
M
Althagafi
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Kelly
http://orcid.org/0000-0002-5333-8860
K
Tai
Toronto General Research Institute, University Health Network, Toronto, Canada.
Sharon J
SJ
Hyduk
Toronto General Research Institute, University Health Network, Toronto, Canada.
Kateryna O
KO
Cybulsky
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Sherine
S
Ensan
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Angela
A
Li
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Rickvinder
R
Besla
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Henry M
HM
Becker
Toronto General Research Institute, University Health Network, Toronto, Canada.
Haiyan
H
Xiao
Center for Immunity and Infection Lausanne, Department of Biochemistry, University of Lausanne, Switzerland.
Sanjiv A
SA
Luther
Krembil Research Institute, University Health Network, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
Robert D
RD
Inman
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Clinton S
CS
Robbins
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Jenny
J
Jongstra-Bilen
Toronto General Research Institute, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Department of Immunology, University of Toronto, Toronto, Canada.
Myron I
MI
Cybulsky
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D054415:Chemokine CCL19 / Q000378:metabolism*; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D023502:Chlamydia muridarum / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D054400:Receptors, CCR7 / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration; D017539:Tunica Intima / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology
D039521:CD11c Antigen; D054415:Chemokine CCL19; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D054400:Receptors, CCR7; D051193:Toll-Like Receptors
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