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  • Gut-educated IgA plasma cel...
    Fitzpatrick, Zachary; Frazer, Gordon; Ferro, Ashley; Clare, Simon; Bouladoux, Nicolas; Ferdinand, John; Tuong, Zewen Kelvin; Negro-Demontel, Maria Luciana; Kumar, Nitin; Suchanek, Ondrej; Tajsic, Tamara; Harcourt, Katherine; Scott, Kirsten; Bashford-Rogers, Rachel; Helmy, Adel; Reich, Daniel S; Belkaid, Yasmine; Lawley, Trevor D; McGavern, Dorian B; Clatworthy, Menna R

    Nature (London), 11/2020, Volume: 587, Issue: 7834
    Journal Article

    The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges-the membranes that surround the brain and spinal cord-contain a diverse population of immune cells . So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positioned adjacent to dural venous sinuses: regions of slow blood flow with fenestrations that can potentially permit blood-borne pathogens to access the brain . Peri-sinus IgA plasma cells increased with age and following a breach of the intestinal barrier. Conversely, they were scarce in germ-free mice, but their presence was restored by gut re-colonization. B cell receptor sequencing confirmed that meningeal IgA cells originated in the intestine. Specific depletion of meningeal plasma cells or IgA deficiency resulted in reduced fungal entrapment in the peri-sinus region and increased spread into the brain following intravenous challenge, showing that meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface.