Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Samantha J. Dando, Renee Kazanis, Holly R. Chinnery, Paul G. McMenamin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The central nervous system (CNS) is considered to be immune privileged, owing in part to the absence of major histocompatibility (MHC) class II+ cells in the healthy brain parenchyma. However, systemic inflammation can activate microglia to express MHC class II, suggesting that systemic inflammation may be sufficient to mature microglia into functional antigen presenting cells (APCs). We examined the effects of systemic lipopolysaccharide (LPS)-induced inflammation on the phenotype and function of putative APCs within the mouse brain parenchyma, as well as its supporting tissues—the choroid plexus and meninges. Microglia isolated from different regions of the brain demonstrated significant heterogeneity in their ability to present antigen to naïve OT-II CD4+ T cells following exposure to systemic LPS. Olfactory bulb microglia (but not cortical microglia) intimately interacted with T cells in vivo and stimulated T cell proliferation in vitro, albeit in the absence of co-stimulation. In contrast, myeloid cells within the choroid plexus and meninges were immunogenic and upregulated the co-stimulatory molecule CD80 following systemic inflammation. Dural APCs, which clustered around LYVE-1+ lymphatics, were more efficient at stimulating naïve T cell proliferation than choroid plexus APCs, suggesting that the dura may be an under-appreciated site for immune interactions. This study has highlighted the functional diversity of myeloid cells within the sub-compartments of the CNS and its supporting tissues. Furthermore, these findings demonstrate that systemic inflammation can mature selected microglia populations and choroid plexus/meningeal myeloid cells into functional APCs, which may contribute to the pathogenesis of neuroinflammation and neurodegenerative diseases.

Original languageEnglish
Pages (from-to)935-949
Number of pages15
JournalGLIA
Volume67
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • antigen presenting cells
  • brain parenchyma
  • central nervous system
  • meninges
  • microglia

Cite this

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title = "Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges",
abstract = "The central nervous system (CNS) is considered to be immune privileged, owing in part to the absence of major histocompatibility (MHC) class II+ cells in the healthy brain parenchyma. However, systemic inflammation can activate microglia to express MHC class II, suggesting that systemic inflammation may be sufficient to mature microglia into functional antigen presenting cells (APCs). We examined the effects of systemic lipopolysaccharide (LPS)-induced inflammation on the phenotype and function of putative APCs within the mouse brain parenchyma, as well as its supporting tissues—the choroid plexus and meninges. Microglia isolated from different regions of the brain demonstrated significant heterogeneity in their ability to present antigen to na{\"i}ve OT-II CD4+ T cells following exposure to systemic LPS. Olfactory bulb microglia (but not cortical microglia) intimately interacted with T cells in vivo and stimulated T cell proliferation in vitro, albeit in the absence of co-stimulation. In contrast, myeloid cells within the choroid plexus and meninges were immunogenic and upregulated the co-stimulatory molecule CD80 following systemic inflammation. Dural APCs, which clustered around LYVE-1+ lymphatics, were more efficient at stimulating na{\"i}ve T cell proliferation than choroid plexus APCs, suggesting that the dura may be an under-appreciated site for immune interactions. This study has highlighted the functional diversity of myeloid cells within the sub-compartments of the CNS and its supporting tissues. Furthermore, these findings demonstrate that systemic inflammation can mature selected microglia populations and choroid plexus/meningeal myeloid cells into functional APCs, which may contribute to the pathogenesis of neuroinflammation and neurodegenerative diseases.",
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Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges. / Dando, Samantha J.; Kazanis, Renee; Chinnery, Holly R.; McMenamin, Paul G.

In: GLIA, Vol. 67, No. 5, 05.2019, p. 935-949.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

AU - Dando, Samantha J.

AU - Kazanis, Renee

AU - Chinnery, Holly R.

AU - McMenamin, Paul G.

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