CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain

Abstract

The CD11c enhanced yellow fluorescent protein (EYFP) transgenic mouse was constructed to identify dendritic cells in the periphery (Lindquist et al. [2004] Nat. Immunol. 5:1243-1250). In this study, we used this mouse to characterize dendritic cells within the CNS. Our anatomic results showed discrete populations of EYFP(+) brain dendritic cells (EYFP(+) bDC) that colocalized with a small fraction of microglia immunoreactive for Mac-1, Iba-1, CD45, and F4/80 but not for NeuN, Dcx, NG2 proteoglycan, or GFAP. EYFP(+) bDC, isolated by fluorescent activated cell sorting (FACS), expressed mRNA for the Itgax (CD11c) gene, whereas FACS anlaysis of EYFP(+) bDC cultures revealed the presence of CD11c protein. Light microscopy studies revealed that EYFP(+) bDC were present in the embryonic CNS when the blood-brain barrier is formed and postnatally when brain cells are amenable to culturing. In adult male mice, EYFP(+) bDC distribution was prominent within regions of the CNS that 1) are subject to structural plasticity and neurogenesis, 2) receive sensory and humoral input from the external environment, and 3) lack a blood-brain barrier. Ultrastructural analysis of EYFP(+) bDC in adult neurogenic niches showed their proximity to developing neurons and a morphology characteristic of immune/microglia cells. Kainic acid-induced seizures revealed that EYFP(+) bDC responded to damage of the hippocampus and displayed morphologies similar to those described for seizure-activated EGFP(+) microglia in the hippocampus of cfms (CSF-1R) EGFP mice. Collectively, these findings suggest a new member of the dendritic cell family residing among the heterogeneous microglia population.

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

“…Recent data have also revealed that cells expressing CD11c are localized within the juxtavascular parenchyma of the healthy mouse brain and extend processes to the glia limitans (astrocytic foot processes at the parenchymal basement membrane, surrounding the brain under the pia mater) (85). In agreement with a previous study (86), this raises the possibility that dendritic cells, which are characterized by high-level CD11c expression, may reside within the brain parenchyma. However, a which consist of the dura mater, arachnoid mater, and pia mater, protect the brain.…”

“…Group B streptococcus and E. coli are common causes of meningitis in neonates (45,46), with group B streptococcus accounting for 86.1% of bacterial meningitis cases in patients of Ͻ2 months of age (14). Gram-negative aerobic bacteria, such as Klebsiella pneumoniae, Serratia marcescens, Salmonella spp., and Pseudomonas aeruginosa, can occasionally be responsible for meningitis in certain patient groups, including infants and patients with head injuries or those undergoing postneurosurgical procedures or immunosuppression (31,47,48).…”

Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells

“…In the LNs of these mice, DCs are the major YFP + population (38). One day after transfer, we immunized CD11c-YFP mice with ova + alum and either BSA or DNase.…”

Visualizing dendritic cell migration within the skin

“…These mice have not only greatly improved our understanding of the behavior of endogenous DCs in the LN (Lindquist et al 2004;Shakhar et al 2005), but also their roles in various models of infection (Aoshi et al 2008;Hapfelmeier et al 2008;Veres et al 2007). They also enabled the visualization of intestinal DCs (Flores-Langarica et al 2005) and the identiWcation of a previously uncharacterized population of DCs in the brain (Bulloch et al 2008). In the skin of these mice, both LCs and DDCs express the transgene (although expression is generally higher in DDCs compared to LCs), and can therefore be identiWed with minimal sample preparation (Ng et al 2008).…”