title: Retinal dendritic cell recruitment, but not function, was inhibited in MyD88 and TRIF deficient mice.
abstract: BACKGROUND
  Immune system cells are known to affect loss of neurons due to injury or disease. Recruitment of immune cells following retinal/CNS injury has been shown to affect the health and survival of neurons in several models. We detected close, physical contact between dendritic cells and retinal ganglion cells following an optic nerve crush, and sought to understand the underlying mechanisms.
  
  
  METHODS
  CD11c-DTR/GFP mice producing a chimeric protein of diphtheria toxin receptor (DTR) and GFP from a transgenic CD11c promoter were used in conjunction with mice deficient in MyD88 and/or TRIF. Retinal ganglion cell injury was induced by an optic nerve crush, and the resulting interactions of the GFPhi cells and retinal ganglion cells were examined.
  
  
  RESULTS
  Recruitment of GFPhi dendritic cells to the retina was significantly compromised in MyD88 and TRIF knockout mice. GFPhi dendritic cells played a significant role in clearing fluorescent-labeled retinal ganglion cells post-injury in the CD11c-DTR/GFP mice. In the TRIF and MyD88 deficient mice, the resting level of GFPhi dendritic cells was lower, and their influx was reduced following the optic nerve crush injury. The reduction in GFPhi dendritic cell numbers led to their replacement in the uptake of fluorescent-labeled debris by GFPlo microglia/macrophages. Depletion of GFPhi dendritic cells by treatment with diphtheria toxin also led to their displacement by GFPlo microglia/macrophages, which then assumed close contact with the injured neurons.
  
  
  CONCLUSIONS
  The contribution of recruited cells to the injury response was substantial, and regulated by MyD88 and TRIF. However, the presence of these adaptor proteins was not required for interaction with neurons, or the phagocytosis of debris. The data suggested a two-niche model in which resident microglia were maintained at a constant level post-optic nerve crush, while the injury-stimulated recruitment of dendritic cells and macrophages led to their transient appearance in numbers equivalent to or greater than the resident microglia.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Heuss
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pierson
authors.forename: Kim Ramil C
authors.initials: KR
authors.lastname: Montaniel
authors.forename: Scott W
authors.initials: SW
authors.lastname: McPherson
authors.forename: Ute
authors.initials: U
authors.lastname: Lehmann
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Hussong
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ferrington
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
authors.affiliation: Department of Ophthalmology & Visual Neurosciences, University of Minnesota, Lions Research Bldg, Rm 314, 2001 6th St SE, Minneapolis 55455, MN, USA. grege001@umn.edu.
authors.forename: Dale S
authors.initials: DS
authors.lastname: Gregerson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D004167:Diphtheria Toxin / Q000494:pharmacology; D004195:Disease Models, Animal; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D022423:Myeloid Cells / Q000502:physiology; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency* / Q000235:genetics; D020221:Optic Nerve Injuries / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014795:Visual Pathways / Q000473:pathology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D039521:CD11c Antigen; D004167:Diphtheria Toxin; D066257:Heparin-binding EGF-like Growth Factor; D053594:Myeloid Differentiation Factor 88; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C036763:monocyte-macrophage differentiation antigen