Differential Phagocytic Properties of CD45low Microglia and CD45high Brain Mononuclear Phagocytes—Activation and Age-Related Effects

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 major...

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Published inFrontiers in immunology Vol. 9; p. 405
Main Authors Rangaraju, Srikant, Raza, Syed Ali, Li, Noel Xiang’An, Betarbet, Ranjita, Dammer, Eric B., Duong, Duc, Lah, James J., Seyfried, Nicholas T., Levey, Allan I.
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LanguageEnglish
Published Frontiers Media S.A 02.03.2018
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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+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 and pathologically unique 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 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 aging. Our data suggest an overall pro-phagocytic and protective role for CD11b+CD45high CNS MPs in neurodegeneration, which if promoted, could be beneficial.
AbstractList 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 and pathologically unique 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 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 aging. Our data suggest an overall pro-phagocytic and protective role for CD11b+CD45high CNS MPs in neurodegeneration, which if promoted, could be beneficial.
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.
Author Duong, Duc
Lah, James J.
Raza, Syed Ali
Dammer, Eric B.
Seyfried, Nicholas T.
Levey, Allan I.
Li, Noel Xiang’An
Rangaraju, Srikant
Betarbet, Ranjita
AuthorAffiliation 2 Department of Chemistry, Emory University , Atlanta, GA , United States
1 Department of Neurology, Emory University , Atlanta, GA , United States
3 Department of Biochemistry, Emory University , Atlanta, GA , United States
AuthorAffiliation_xml – name: 3 Department of Biochemistry, Emory University , Atlanta, GA , United States
– name: 2 Department of Chemistry, Emory University , Atlanta, GA , United States
– name: 1 Department of Neurology, Emory University , Atlanta, GA , United States
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  fullname: Rangaraju, Srikant
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  givenname: Noel Xiang’An
  surname: Li
  fullname: Li, Noel Xiang’An
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Edited by: Uday Kishore, Brunel University London, United Kingdom
Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
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Reviewed by: Raymond B. Birge, Rutgers University, The State University of New Jersey, United States; Robert Adam Harris, Karolinska Institute (KI), Sweden
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Snippet In the central nervous system (CNS), microglia are innate immune mononuclear phagocytes (CNS MPs) that can phagocytose infectious particles, apoptotic cells,...
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StartPage 405
SubjectTerms Alzheimer’s disease
CNS mononuclear phagocytes
flow cytometry
Immunology
neuroinflammation
phagocytosis
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Title Differential Phagocytic Properties of CD45low Microglia and CD45high Brain Mononuclear Phagocytes—Activation and Age-Related Effects
URI https://search.proquest.com/docview/2015414719
https://pubmed.ncbi.nlm.nih.gov/PMC5840283
https://doaj.org/article/8a153a6e508f4698bd6e4545af988986
Volume 9
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