A case of mistaken identity: CD11c-eYFP(+) cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells

Glia. 2016 Aug;64(8):1331-49. doi: 10.1002/glia.23005. Epub 2016 May 18.

Abstract

Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331-1349.

Keywords: Crumbs 1; antigen presenting cells; central nervous system; microglia; retinal dystrophic lesions.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Brain / cytology*
  • Brain / metabolism
  • CD11c Antigen / metabolism*
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Immunoenzyme Techniques
  • Leukocyte Common Antigens / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / cytology*
  • Microglia / metabolism
  • Microscopy, Confocal
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Pia Mater / cytology
  • Pia Mater / metabolism
  • Retina / cytology*
  • Retina / metabolism

Substances

  • Bacterial Proteins
  • CD11c Antigen
  • Crb1 protein, mouse
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • yellow fluorescent protein, Bacteria
  • Leukocyte Common Antigens
  • Ptprc protein, mouse