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Front. Immunol. | doi: 10.3389/fimmu.2018.00405

Differential phagocytic properties of CD45low microglia and CD45high brain mononuclear phagocytes - activation and age-related effects

  • 1Emory University, United States

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+CD45low microglia account for the majority of CNS MPs, a small population of CD11b+CD45high CNS MPs is also recognized in AD that surround Aβ plaques. These transcriptionally-distinct and pathologically-relevant CD45high 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+ CD45low and CD45high CNS MPs to phagocytose macroparticles and fAβ under normal, acute and chronic neuroinflammatory states. CD45high CNS MPs also highly upregulate TREM2, CD11c and several disease-associated-microglia (DAM) signature genes, and have a higher phagocytic capacity for Aβ as compared to CD45low microglia in the 5xFAD mouse model of AD that becomes more apparent with ageing. Our data suggest an overall pro-phagocytic and protective role for CD11b+CD45high CNS MPs in neurodegeneration, which if promoted, could be beneficial.

Keywords: CNS mononuclear phagocytes, Phagocytosis, Flow Cytometry, Neuroinflammation, Alzheimer’s disease

Received: 19 Dec 2017; Accepted: 14 Feb 2018.

Edited by:

Uday Kishore, Brunel University, United Kingdom

Reviewed by:

Robert A. Harris, Karolinska Institute (KI), Sweden
Raymond B. Birge, Rutgers University, The State University of New Jersey, United States  

Copyright: © 2018 Rangaraju, Raza, Li, Betarbet, Dammer, Duong, Lah, Seyfried and Levey. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Srikant Rangaraju, Emory University, Atlanta, United States, srikant.rangaraju@emory.edu