Neurons and astrocytes respond to prion infection by inducing microglia recruitment.
The accumulation and activation of microglial cells at sites of amyloid prion deposits or plaques have been documented extensively. Here, we investigate the in vivo recruitment of microglial cells soon after intraocular injection of scrapie-infected cell homogenate (hgtsc+) using immunohistochemistry on retinal sections. A population of CD11b/CD45-positive microglia was specifically detected within the ganglion and internal plexiform retinal cell layers by 2 d after intravitreal injection of hgtsc+. Whereas no chemotactism properties were ascribed to hgtsc+ alone, a massive migration of microglial cells was observed by incubating primary cultured neurons and astrocytes with hgtsc+ in a time- and concentration-dependent manner. hgtsc+ triggered the recruitment of microglial cells by interacting with both neurons and astrocytes by upregulation of the expression levels of a broad spectrum of neuronal and glial chemokines. We show that, in vitro and in vivo, the microglia migration is at least partly under the control of chemokine receptor-5 (CCR-5) activation, because highly specific CCR-5 antagonist TAK-779 significantly reduced the migration rate of microglia. Activated microglia recruited in the vicinity of prion may, in turn, cause neuronal cell damage by inducing apoptosis. These findings provide insight into the understanding of the cell-cell communication that takes place during the development of prion diseases.
Marella
Mathieu
M
Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097, Centre National de la Recherche Scientifique 660, 06560 Valbonne, France.
Chabry
Joëlle
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D019286:Endopeptidase K / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009573:Nitrites / Q000378:metabolism; D009900:Optic Nerve / Q000473:pathology; D018620:PrPSc Proteins / Q000472:pathogenicity / Q000494:pharmacology*; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019713:Receptors, CCR5 / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000473:pathology; D013347:Subcellular Fractions / Q000737:chemistry
D018925:Chemokines; D009573:Nitrites; D018620:PrPSc Proteins; D019713:Receptors, CCR5; D019286:Endopeptidase K