s40478-016-0293-8.pdf 2,32MB
1000 Titel
  • Chronic Toxoplasma gondii infection enhances β-amyloid phagocytosis and clearance by recruited monocytes
1000 Autor/in
  1. Möhle, Luisa |
  2. Israel, Nicole |
  3. Paarmann, Kristin |
  4. Krohn, Markus |
  5. Pietkiewicz, Sabine |
  6. Müller, Andreas |
  7. Lavrik, Inna N. |
  8. Buguliskis, Jeffrey S. |
  9. Schott, Björn |
  10. Schlüter, Dirk |
  11. Gundelfinger, Eckart |
  12. Montag, Dirk |
  13. Seifert, Ulrike |
  14. Pahnke, Jens |
  15. Dunay, Ildiko Rita |
1000 Erscheinungsjahr 2016
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-03-16
1000 Erschienen in
1000 Quellenangabe
  • 4:25
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2016
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Alzheimer's disease (AD) is associated with the accumulation of β-amyloid (Aβ) as senile plaques in the brain, thus leading to neurodegeneration and cognitive impairment. Plaque formation depends not merely on the amount of generated Aβ peptides, but more importantly on their effective removal. Chronic infections with neurotropic pathogens, most prominently the parasite Toxoplasma (T.) gondii, are frequent in the elderly, and it has been suggested that the resulting neuroinflammation may influence the course of AD. In the present study, we investigated how chronic T. gondii infection and resulting neuroinflammation affect plaque deposition and removal in a mouse model of AD. RESULTS: Chronic infection with T. gondii was associated with reduced Aβ and plaque load in 5xFAD mice. Upon infection, myeloid-derived CCR2(hi) Ly6C(hi) monocytes, CCR2(+) Ly6C(int), and CCR2(+) Ly6C(low) mononuclear cells were recruited to the brain of mice. Compared to microglia, these recruited mononuclear cells showed highly increased phagocytic capacity of Aβ ex vivo. The F4/80(+) Ly6C(low) macrophages expressed high levels of Triggering Receptor Expressed on Myeloid cells 2 (TREM2), CD36, and Scavenger Receptor A1 (SCARA1), indicating phagocytic activity. Importantly, selective ablation of CCR2(+) Ly6C(hi) monocytes resulted in an increased amount of Aβ in infected mice. Elevated insulin-degrading enzyme (IDE), matrix metalloproteinase 9 (MMP9), as well as immunoproteasome subunits β1i/LMP2, β2i/MECL-1, and β5i/LMP7 mRNA levels in the infected brains indicated increased proteolytic Aβ degradation. Particularly, LMP7 was highly expressed by the recruited mononuclear cells in the brain, suggesting a novel mechanism of Aβ clearance. CONCLUSIONS: Our results indicate that chronic Toxoplasma infection ameliorates β-amyloidosis in a murine model of AD by activation of the immune system, specifically by recruitment of Ly6C(hi) monocytes and by enhancement of phagocytosis and degradation of soluble Aβ. Our findings provide evidence for a modulatory role of inflammation-induced Aβ phagocytosis and degradation by newly recruited peripheral immune cells in the pathophysiology of AD.
1000 Sacherschließung
lokal Alzheimer’s disease
lokal Toxoplasma gondii
lokal Chronic infection
lokal Aβ clearance
lokal Ly6Chi monocytes
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 Label
1000 Förderer
  1. German research council (DFG) |
1000 Fördernummer
  1. IRD DU1112/3-1; SFB 854
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer German research council (DFG) |
    1000 Förderprogramm -
    1000 Fördernummer IRD DU1112/3-1; SFB 854
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6404317.rdf
1000 Erstellt am 2017-09-07T11:22:01.523+0200
1000 Erstellt von 122
1000 beschreibt frl:6404317
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet Wed Jun 02 07:27:16 CEST 2021
1000 Objekt bearb. Wed Jun 02 07:27:15 CEST 2021
1000 Vgl. frl:6404317
1000 Oai Id
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1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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