CCR2+ monocytes replenish border-associated macrophages in the diseased mouse brain
Lingxiao Wang,
Jiaying Zheng,
Shunyi Zhao,
Yushan Wan,
Meijie Wang,
Dale B. Bosco,
Chia-Yi Kuan,
Jason R. Richardson,
Long-Jun Wu
Affiliations
Lingxiao Wang
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA
Jiaying Zheng
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA
Shunyi Zhao
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA
Yushan Wan
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Meijie Wang
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA
Dale B. Bosco
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Chia-Yi Kuan
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Jason R. Richardson
Department of Environmental Health Science, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA
Long-Jun Wu
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Corresponding author
Summary: Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ monocyte-derived long-lived BAMs in a brain compression model and in a sepsis model after the initial disruption of homeostasis. Our study reveals that the short-lived CCR2+ monocytes transform into long-lived BAM-like cells at the CNS border and subsequently contribute to BAM populations.
