Abstract

Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1+ precursors and postnatally from bone marrow–derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche.

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Acknowledgements

We acknowledge the administrative assistance of B. Bali. Supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award (MSH136670), a CIHR operating grant (MOP133390), an Ontario Lung Association/Pfizer Award and the Peter Munk Chair in Aortic Disease Research (C.S.R.) and an Ontario Graduate Scholarship (S.E.).

Author information

Author notes

    • Sherine Ensan
    • , Angela Li
    •  & Rickvinder Besla

    These authors contributed equally to this work.

Affiliations

  1. Department of Immunology, University of Toronto, Toronto, Ontario, Canada.

    • Sherine Ensan
    • , Angela Li
    • , Mahmoud El-Maklizi
    • , Kaveh Farrokhi
    • , Gary A Levy
    • , Slava Epelman
    •  & Clinton S Robbins
  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

    • Rickvinder Besla
    • , Eric A Shikatani
    • , Mansoor Husain
    • , Myron I Cybulsky
    •  & Clinton S Robbins
  3. Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.

    • Norbert Degousee
    • , Jake Cosme
    • , Mark Roufaiel
    • , Lauren Robins
    • , Cedric Li
    • , Bonnie Lewis
    • , Ramzi Khattar
    • , John Byrne
    • , Maral Ouzounian
    • , Caleb C J Zavitz
    • , Gary A Levy
    • , Mansoor Husain
    • , Slava Epelman
    • , Anthony O Gramolini
    • , Myron I Cybulsky
    • , Barry B Rubin
    •  & Clinton S Robbins
  4. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Jesse W Williams
    •  & Gwendalyn J Randolph
  5. Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, Quebec, Canada.

    • Tae Jin Yun
    • , Jun Seong Lee
    •  & Cheolho Cheong
  6. Institute of Neuropathology and Faculty of Biology, University of Freiburg, Freiburg, Germany.

    • Peter Wieghofer
  7. Hoffmann-La Roche, pRED, Pharma Research and Early Development, DTA Inflammation, Nutley, New Jersey, USA.

    • Carla M T Bauer
  8. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Peter Libby
  9. Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston,MA, USA.

    • Filip K Swirski
  10. Institute of Neuropathology and BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.

    • Marco Prinz
  11. Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany.

    • Ingo Hilgendorf
  12. Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.

    • Anthony O Gramolini
  13. Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.

    • John Byrne
    • , Maral Ouzounian
    • , Mansoor Husain
    • , Slava Epelman
    • , Anthony O Gramolini
    • , Myron I Cybulsky
    • , Barry B Rubin
    •  & Clinton S Robbins

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Contributions

S.E., A.L. and R.B. conceived the project, designed and performed experiments and analyzed and interpreted data. N.D., J.C., M.R., M.E.M., J.W., E.S., C.L., B.L., L.R., T.J.Y., J.S.L., P.W., I.H., S.E., R.K. and K.F. performed experiments and helped interpret the data. M.O., J.B., C.C.J.Z., G.A.L., C.M.T.B., P.L., M.H., F.K.S., C.C., M.P., I.H., G.J.R., S.E., A.O.G., M.C. and B.B.R. provided materials and intellectual input and edited the manuscript. C.S.R. conceived the project, designed and performed experiments, supervised the study and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Clinton S Robbins.

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DOI

https://doi.org/10.1038/ni.3343