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Author Notes:

Correspondence: Srikant Rangaraju srikant.rangaraju@emory.edu

SR and SAR have conceptualized and executed all experiments, analyzed data, written this manuscript, and equally contributed to the work.

RB and NL have performed experiments, analyzed data and critically reviewed and revised the manuscript.

ED and DD performed proteomic studies and analyzed data.

NS, JL, and AL have reviewed and discussed the results and have edited the manuscript.

The authors thank Dr. David Lynn (Professor, Department of Chemistry, Emory University, Atlanta) for feedback on this manuscript and Robert E. Karaffa II for assistance with flow cytometric studies.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Institutional Animal Care and Use Committee approval was obtained prior to in vivo work and all work was performed in strict accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

Subjects:

Research Funding:

This work was supported by: Emory Alzheimer’s Disease Research Center Grant (P50 AG025688), American Brain Foundation Award (#00042351), NINDS K08 (NS099474-1), Emory Neuroscience NINDS Core facilities grant (P30 NS055077), 1U01AG046161, NSF CHE-1507932, and NSF/DMR-BSF 1610377.

The work was also supported by the Emory flow cytometry core facility.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • CNS mononuclear phagocytes
  • phagocytosis
  • flow cytometry
  • neuroinflammation
  • Alzheimer's disease
  • ALZHEIMERS-DISEASE
  • MOUSE MODELS
  • ACTIN CYTOSKELETON
  • AMYLOID PLAQUES
  • TRANSGENIC MICE
  • RECEPTOR
  • MACROPHAGES
  • CELLS
  • FC
  • NEURODEGENERATION

Differential Phagocytic Properties of CD45(low) Microglia and CD45(high) Brain Mononuclear Phagocytes-Activation and Age-Related Effects

Tools:

Journal Title:

Frontiers in Immunology

Volume:

Volume 9, Number MAR

Publisher:

, Pages 405-405

Type of Work:

Article | Final Publisher PDF

Abstract:

In the central nervous system (CNS), microglia are innate immune mononuclear phagocytes (CNS MPs) that can phagocytose infectious particles, apoptotic cells, neurons, and pathological protein aggregates, such as Aβ in Alzheimer's disease (AD). While CD11b + CD45 low microglia account for the majority of CNS MPs, a small population of CD11b + CD45 high CNS MPs is also recognized in AD that surround Aβ plaques. These transcriptionally and pathologically unique CD45 high cells have unclear origin and undefined phagocytic characteristics. We have comprehensively validated rapid flow cytometric assays of bulk-phase and amyloid β fibril (fAβ) phagocytosis and applied these to study acutely isolated CNS MPs. Using these methods, we provide novel insights into differential abilities of CD11b + CD45 low and CD45 high CNS MPs to phagocytose macroparticles and fAβ under normal, acute, and chronic neuroinflammatory states. CD45 high CNS MPs also highly upregulate TREM2, CD11c, and several disease-associated microglia signature genes and have a higher phagocytic capacity for Aβ as compared to CD45 low microglia in the 5xFAD mouse model of AD that becomes more apparent with aging. Our data suggest an overall pro-phagocytic and protective role for CD11b + CD45 high CNS MPs in neurodegeneration, which if promoted, could be beneficial.

Copyright information:

© 2018 Rangaraju, Raza, Li, Betarbet, Dammer, Duong, Lah, Seyfried and Levey.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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