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Differential Phagocytic Properties of CD45low Microglia and CD45high Brain Mononuclear Phagocytes-Activation and

Srikant Rangaraju1, Syed Ali Raza1, Noel Xiang'An Li2

  • 1Department of Neurology, Emory University, Atlanta, GA, United States.

Frontiers in Immunology
|March 20, 2018
PubMed

Insights

In Alzheimer's disease (AD), a unique CD45high microglia population shows enhanced amyloid-beta (Aβ) phagocytosis. These cells may play a protective role in neurodegeneration, offering a potential therapeutic target.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are key immune cells in the central nervous system (CNS).
  • A distinct CD11b+CD45high microglia subset exists in Alzheimer's disease (AD) brains.
  • The origin and function of CD45high microglia, particularly their phagocytic capacity, remain unclear.

Purpose of the Study:

  • To characterize the phagocytic abilities of CD11b+CD45low and CD11b+CD45high microglia.
  • To investigate the role of CD45high microglia in Alzheimer's disease pathogenesis.
  • To validate flow cytometry assays for studying microglia phagocytosis.

Main Methods:

  • Development and validation of rapid flow cytometric assays for bulk-phase and amyloid-beta fibril (fAβ) phagocytosis.
  • Acute isolation and analysis of CNS myeloid phagocytes (MPs) from the 5xFAD mouse model of AD.
  • Comparative analysis of phagocytic capacity between CD45low and CD45high microglia under varying neuroinflammatory conditions.

Main Results:

  • CD45high CNS MPs demonstrate significantly higher phagocytic capacity for Aβ compared to CD45low microglia, especially in aging 5xFAD mice.
  • CD45high microglia upregulate TREM2, CD11c, and disease-associated microglia genes.
  • Differential phagocytic abilities of CD45low and CD45high CNS MPs were observed for macroparticles and fAβ.

Conclusions:

  • CD11b+CD45high CNS MPs exhibit a pro-phagocytic role, particularly for Aβ clearance in AD.
  • These cells display characteristics suggesting a protective function in neurodegeneration.
  • Targeting or promoting CD45high microglia activity could offer a therapeutic strategy for AD.
Keywords:
Alzheimer’s diseaseCNS mononuclear phagocytesflow cytometryneuroinflammationphagocytosis

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