Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges
Samantha J. Dando1, Renee Kazanis1, Holly R. Chinnery2, Paul G. McMenamin1
1Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia; 2Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia
The 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, peripheral inflammation can activate microglia to express MHC class II, suggesting that peripheral inflammation may be sufficient to mature microglia into functional antigen presenting cells (APCs). We examined the effects of peripheral 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 mouse brain parenchyma 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, immune cells within the choroid plexus and meninges were immunogenic and upregulated the co-stimulatory molecule CD80 following peripheral inflammation. Dural APCs, which clustered around LYVE-1+ lymphatics, were more efficient at stimulating naïve T cell proliferation than choroid plexus APCs and also spleen APCs, suggesting that the dura may be an under-appreciated site for immune interactions. The results of this study highlight the functional diversity of immune cells within the sub-compartments of the CNS and its supporting tissues. Furthermore, these data demonstrate that peripheral inflammation induced by systemic LPS can mature selected microglia populations and choroid plexus/meningeal immune cells into functional APCs, which may contribute to the pathogenesis of neuroinflammation and neurodegenerative diseases.